Characterization of the complete chloroplast genome sequence of Bassia scoparia (L.) A. J. Scott 1978 (Amaranthaceae) and its phylogenetic analysis.

Bassia scoparia, an annual potherb belonging to the family Amaranthaceae, has been widely used in traditional Chinese and Japanese medicine for over 2000 years. Herein, we presented its complete chloroplast. The chloroplast genome sequence was 151,278 bp in length with a 36.6% content of GC. The genome showed the typical quadripartite structure, comprising a pair of inverted repeat (IR) regions (24,353 bp) separated by a large single-copy (LSC) region (84,067 bp) and a small single-copy (SSC) region (18,505 bp). This chloroplast genome harbored 133 predicted genes, including 88 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The phylogenetic analysis indicated that B. scoparia was closely related to B. littorea. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Bassia but also provides valuable insights for the evolutionary study of the family Amaranthaceae.

BeEAM vs. BEAM: evaluating conditioning regimens for autologous stem cell transplantation in patients with relapsed or refractory DLBCL.

PURPOSE: To evaluate whether BeEAM is an alternative to BEAM for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). METHODS: Data of 60 patients with relapsed or refractory DLBCL who underwent ASCT from January 2018 to June 2023 in our center, including 30 patients in the BeEAM group and 30 patients in the BEAM group, were retrospectively analyzed. The time to hematopoietic reconstitution, treatment-related adverse events, number of hospitalization days, hospitalization cost, and survival benefit were compared between the two groups. RESULTS: The clinical characteristics of the patients did not significantly differ between the two groups. The median number of reinfused CD34 + cells was 5.06 × 106/kg and 5.17 × 106/kg in the BeEAM and BEAM groups, respectively, which did not significantly different (p = 0.8829). In the BeEAM and BEAM groups, the median time to neutrophil implantation was 10.2 and 10.27 days, respectively (p = 0.8253), and the median time to platelet implantation was 13.23 and 12.87 days, respectively (p = 0.7671). In the BeEAM and BEAM groups, the median hospitalization duration was 30.37 and 30.57 days, respectively (p = 0.9060), and the median hospitalization cost was RMB 83,425 and RMB 96,235, respectively (p = 0.0560). The hospitalization cost was lower in the BeEAM group. The most common hematologic adverse events were grade ≥ 3 neutropenia and thrombocytopenia, whose incidences were similar in the two groups. The most common non-hematologic adverse events were ≤ grade 2 and the incidences of these events did not significantly differ between the two groups. Median overall survival was not reached in either group, with predicted 5-year overall survival of 72.5% and 60% in the BeEAM and BEAM groups, respectively (p = 0.5872). Five-year progression-free survival was 25% and 20% in the BeEAM and BEAM groups, respectively (p = 0.6804). CONCLUSION: As a conditioning regimen for relapsed or refractory DLBCL, BeEAM has a desirable safety profile and is well tolerated, and its hematopoietic reconstitution time, number of hospitalization days, and survival benefit are not inferior to those of BEAM. BeEAM has a lower hospitalization cost and is an alternative to BEAM.

Identification and analysis of novel recessive alleles for Tan1 and Tan2 in sorghum.

Background: The identification and analysis of allelic variation are important bases for crop diversity research, trait domestication and molecular marker development. Grain tannin content is a very important quality trait in sorghum. Higher tannin levels in sorghum grains are usually required when breeding varieties resistant to bird damage or those used for brewing liquor. Non-tannin-producing or low-tannin-producing sorghum accessions are commonly used for food and forage. Tan1 and Tan2, two important cloned genes, regulate tannin biosynthesis in sorghum, and mutations in one or two genes will result in low or no tannin content in sorghum grains. Even if sorghum accessions contain dominant Tan1 and Tan2, the tannin contents are distributed from low to high, and there must be other new alleles of the known regulatory genes or new unknown genes contributing to tannin production. Methods: The two parents 8R306 and 8R191 did not have any known recessive alleles for Tan1 and Tan2, and it was speculated that they probably both had dominant Tan1 and Tan2 genotypes. However, the phenotypes of two parents were different; 8R306 had tannins and 8R191 had non-tannins in the grains, so these two parents were constructed as a RIL population. Bulked segregant analysis (BSA) was used to determine other new alleles of Tan1 and Tan2 or new Tannin locus. Tan1 and Tan2 full-length sequences and tannin contents were detected in wild sorghum resources, landraces and cultivars. Results: We identified two novel recessive tan1-d and tan1-e alleles and four recessive Tan2 alleles, named as tan2-d, tan2-e, tan2-f, and tan2-g. These recessive alleles led to loss of function of Tan1 and Tan2, and low or no tannin content in sorghum grains. The loss-of-function alleles of tan1-e and tan2-e were only found in Chinese landraces, and other alleles were found in landraces and cultivars grown all around the world. tan1-a and tan1-b were detected in foreign landraces, Chinese cultivars and foreign cultivars, but not in Chinese landraces. Conclusion: These results implied that Tan1 and Tan2 recessive alleles had different geographically distribution in the worldwide, but not all recessive alleles had been used in breeding. The discovery of these new alleles provided new germplasm resources for breeding sorghum cultivars for food and feed, and for developing molecular markers for low-tannin or non-tannin cultivar-assisted breeding in sorghum.

New findings on CD16brightCD62Ldim neutrophil subtypes in sepsis-associated ARDS: an observational clinical study.

Background: The CD16brightCD62Ldim neutrophil subtype is a recently identified neutrophil subtype. The aim of this study was to evaluate changes of peripheral blood CD16brightCD62Ldim neutrophils in patients with sepsis-associated ARDS. Methods: We prospectively recruited adult patients with sepsis-associated ARDS in the intensive care unit (ICU). Patient demographic data, medical history information, and laboratory data were collected within 48 hours of enrollment, and flow cytometry was applied to analyze the CD16brightCD62Ldim neutrophil subtype in the patients' peripheral blood. Multifactor COX regression models were used to analyze factors affecting prognosis, and Spearman correlation coefficients were used to analyze clinical and laboratory indicators affecting complications of infection. Results: Of the 40 patients, 9 patients died by the 28-day follow-up, indicating a mortality rate of 22.5%. Patients in the nonsurvival group had higher CD16brightCD62Ldim neutrophil levels. Patients with sepsis-associated ARDS who had a baseline proportion of CD16brightCD62Ldim neutrophil subtypes to total neutrophils in peripheral blood >3.73% had significantly higher 28-day mortality, while patients with CD16brightCD62Ldim neutrophil subtypes counts >2.62×109/L were also associated with significantly higher 28-day mortality. The percentage of the CD16brightCD62Ldim neutrophil subtype (HR=5.305, 95% CI 1.986-14.165, p=0.001) and IL-8 (HR=3.852, 95% CI 1.561-9.508, p=0.003) were independent risk factors for the development of infectious complications in patients with sepsis-related ARDS. The percentage of CD16brightCD62Ldim neutrophil subtypes predicted an AUC of 0.806 (95% CI 0.147-0.964, P=0.003) for the development of infectious complications, and 0.742 (95% CI 0.589-0.895, P=0.029) for the prediction of death within 28 days. Conclusion: We identified for the first time that CD16brightCD62Ldim neutrophils are elevated in patients with sepsis-associated ARDS and are associated with infectious complications and poor prognosis. The percentage of CD16brightCD62Ldim neutrophil subtypes may serve as a predictor of the development of infectious complications in patients with ARDS.

First Report of Powdery Mildew on Cardamine violifolia in China.

Cardamine violifolia, also called Cardamine hupingshanensis, is an economically important medicinal plant renowned for accumulating selenium (Guo et al., 2022). Selenium is an essential trace element with anti-oxidant, anti-inflammatory, anti-cancer, and immune regulatory functions. In July 2023, an outbreak of powdery mildew was detected, infecting the leaves of numerous C. violifolia plants in Enshi (30°11'5.27''N; 109°48'48.45''E), Hubei Province, China. This disease caused severe damage to plant leaves and stems, starting as individual spots and merging into a large mold that covers the entire leaf. It affected nearly 25% all C. violifolia plants, resulting in significant yield loss, disruption of normal metabolism, and premature aging. The lower leaf blades and underside of the leaves were particularly vulnerable. The affected leaves were collected and subjected to morphological diagnostic analysis (Mori et al., 2000) (Fig. S1). The powdery mildew species aggressively spread throughout the leaves, pedicels, and pods, persisting until present and often covering the entire surface. The conidiophores were upright, cylindrical, composed of 3 to 4 cells, and measured 92.3 ± 12.9 × 9.2 ± 0.6 µm (n = 30). Conidial pedicels had 21.6 ± 3.4 µm (n = 50) long cylindrical podocytes. The monoconidia were columnar or barrel-columnar, 30.60-55.59 × 9.11-20.00 µm in size. Conidia lacked an obvious cellulose body. The bud tubes formed from the end of conidia, and papillary appressoria developed on the epiphytic mycelia. ITS region sequences were amplified using the specific powdery mildew universal primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3'), PM6 (5'-GYCRCYCTGTCGCGAG-3') for partial sequences of 18S and 28S ribosomal DNA genes (Takamatsu et al., 2001). The sequence was deposited in the GenBank under the accession number OR506156 and aligned with available sequences on NCBI, which were 99.2%(528/532) identical to the E. cruciferarum (MT309701, MF192845, and KY660929) sequences (Fig. S2). The ITS sequence from GenBank was used to conduct maximum likelihood phylogenetic analysis using MEGA 11.0. The analysis results showed both the strain and E. cruciferarum clustered on the same branch. To confirm Koch's postulates, pathogenicity testing was carried out using an illuminating incubator. Infected leaves were attached to healthy leaves of C. violifolia seedlings (n=8). All the plants were incubated under 25℃ and >80% relative humidity. After one month, all inoculated plants presented the same symptoms as those initially observed in the field. Morphological and molecular analysis confirmed the isolated fungi's identity as the same pathogen. Therefore, C. violifolia is a suitable host for E. cruciferarum in China. The growers must be informed of these findings to prevent serious economic losses caused by this pathogenic white powder and to prepare for proper management practices. To our knowledge, this is the first report of E. cruciferarum infecting C. violifolia in China.

Microfluidics-Derived Microparticles with Prebiotics and Probiotics for Enhanced In Situ Colonization and Immunoregulation of Colitis.

Oral administration of probiotics orchestrates the balance between intestinal microbes and the immune response. However, effective delivery and in situ colonization are limited by the harsh environment of the gastrointestinal tract. Herein, we provide a microfluidics-derived encapsulation strategy to address this problem. A novel synergistic delivery system composed of EcN Nissle 1917 and prebiotics, including alginate sodium and inulin gel, for treating inflammatory bowel disease and colitis-associated colorectal cancer is proposed. We demonstrated that EcN@AN microparticles yielded promising gastrointestinal resistance for on-demand probiotic delivery and colon-retentive capability. EcN@AN microparticles efficiently ameliorated intestinal inflammation and modulated the gut microbiome in experimental colitis. Moreover, the prebiotic composition of EcN@AN enhanced the fermentation of relative short-chain fatty acid metabolites, a kind of postbiotics, to exert anti-inflammatory and tumor-suppressive effects in murine models. This microfluidcis-based approach for the coordinated delivery of probiotics and prebiotics may have broad implications for gastrointestinal bacteriotherapy applications.

Fluidization and Application of Carbon Nano Agglomerations.

Carbon nanomaterials are unique with excellent functionality and diverse structures. However, agglomerated structures are commonly formed because of small-size effects and surface effects. Their hierarchical assembly into micro particles enables carbon nanomaterials to break the boundaries of classical Geldart particle classification before stable fluidization under gas-solid interactions. Currently, there are few systematic reports regarding the structural evolution and fluidization mechanism of carbon nano agglomerations. Based on existing research on carbon nanomaterials, this article reviews the fluidized structure control and fluidization principles of prototypical carbon nanotubes (CNTs) as well as their nanocomposites. The controlled agglomerate fluidization technology leads to the successful mass production of agglomerated and aligned CNTs. In addition, the self-similar agglomeration of individual ultralong CNTs and nanocomposites with silicon as model systems further exemplify the important role of surface structure and particle-fluid interactions. These emerging nano agglomerations have endowed classical fluidization technology with more innovations in advanced applications like energy storage, biomedical, and electronics. This review aims to provide insights into the connections between fluidization and carbon nanomaterials by highlighting their hierarchical structural evolution and the principle of agglomerated fluidization, expecting to showcase the vitality and connotation of fluidization science and technology in the new era.

Insights into the SiO2 Stress Effect on the Electrochemical Performance of Si anode.

Silicon (Si) is regarded as the most potential anode material for next-generation lithium-ion batteries (LIBs). However, huge volume expansion hinders its commercial application. Here, a yolk-shell structural nitrogen-doped carbon coated Si@SiO2 is prepared by SiO2 template and HF etching method. The as-prepared composite exhibits superior cycling stability with a high reversible capacity of 577 mA h g-1 at 1 A g-1 after 1000 cycles. The stress effect of SiO2 on stabilizing the electrochemical performance of Si anode is systematically investigated for the first time. In situ thickness measurement reveals that the volume expansion thickness of Si@SiO2 upon charge-discharge is obviously smaller than Si, demonstrating the electrode expansion can be effectively inhibited to improve the cyclability. The density functional theory (DFT) calculation further demonstrates the moderate young's modulus and enhanced hardness after SiO2 coating contribute significantly to the mechanical reinforcement of overall Si@SiO2@void@NC composite. Various post-cycling electrode analyses also address the positive effects of inner stress from the Si core on effectively relieving the damage to electrode structure, facilitating the formation of a more stable inorganic-rich solid electrolyte interphase (SEI) layer. This study provides new insights for mechanical stability and excellent electrochemical performance of Si-based anode materials.

Surgical Management and Outcome of Entero-Urinary Fistula Complicating Crohn's Disease: A Single Center Study.

BACKGROUND: Entero-urinary fistulas (EUF) are a rare complication of Crohn's disease (CD), observed in 1.6 to 7.7%. The management of EUF complicating CD is challenging. We aimed to report the outcome and surgical management of EUF in CD. METHODS: A retrospective chart review was performed in all CD patients with EUF who underwent surgery in our center between January 2012 and December 2021. Patient demographics, preoperative optimization, surgical management, postoperative complications, and follow-up information were collected from a prospectively maintained database. RESULTS: A total of 74 eligible patients were identified. The median interval between CD diagnosis and EUF diagnosis was 2 (0.08-6.29) years. Patients with EUF presented with pneumaturia (75.68%), urinary tract infections (72.97%), fecaluria (66.22%), and hematuria (6.76%). Fistulae originated most commonly from the ileum (63.51%), followed by the colon (14.86%), the rectum (9.46%), the cecum (2.70%), and multiple sites (9.46%). The EUF symptoms, weight, nutritional status, laboratory results were significantly improved after preoperative optimization. The absence of EUF symptoms was observed in 42 patients after the optimization and only 9 of which required bladder repair. However, 19 of 32 patients whose symptoms did not resolve required bladder repair (P = 0.001). Only 1 patient developed a bladder leakage in the early postoperative period and 3 patients experienced recurrent bladder fistula. CONCLUSIONS: Surgical management of EUF complicating CD is effective and safe, with a low rate of postoperative complication and EUF recurrence. Preoperative optimization, which is associated with the resolution of urinary symptoms and improved surgical outcomes, should be recommended.

Biodegradable Hollow Nanoscavengers Restore Liver Functions to Reverse Insulin Resistance in Type 2 Diabetes.

Type 2 diabetes (T2D) results from the cells' insulin resistance, and to date, insulin therapy and diabetes medications targeting glycemic management have failed to reverse the increase in T2D prevalence. Restoring liver functions to improve hepatic insulin resistance by reducing oxidative stress is a potential strategy for T2D treatment. Herein, the liver-targeted biodegradable silica nanoshells embedded with platinum nanoparticles (Pt-SiO2) are designed as reactive oxygen species (ROS) nanoscavengers and functional hollow nanocarriers. Then, 2,4-dinitrophenol-methyl ether (DNPME, mitochondrial uncoupler) is loaded inside Pt-SiO2, followed by coating a lipid bilayer (D@Pt-SiO2@L) for long-term effective ROS removal (platinum nanoparticles scavenge overproduced ROS, while DNPME inhibits ROS production) in the liver tissue of T2D models. It is found that D@Pt-SiO2@L reverses elevated oxidative stress, insulin resistance, and impaired glucose consumption in vitro, and significantly improves hepatic steatosis and antioxidant capacity in diabetic mice models induced by a high-fat diet and streptozotocin. Moreover, intravenous administration of D@Pt-SiO2@L indicates therapeutic effects on hyperlipidemia, insulin resistance, hyperglycemia, and diabetic nephropathy, which provides a promising approach for T2D treatment by reversing hepatic insulin resistance through long-term ROS scavenging.

Crohn's disease-associated AIEC inhibiting intestinal epithelial cell-derived exosomal let-7b expression regulates macrophage polarization to exacerbate intestinal fibrosis.

The interaction between adherent-invasive Escherichia coli (AIEC) and intestinal macrophages is implicated in the pathogenesis of Crohn's disease (CD). However, its role in intestinal fibrogenesis and the underlying molecular mechanisms are poorly understood. In addition, miRNAs such as let-7b may participate in AIEC-macrophage interactions. In this study, we identified that the colonization of AIEC in the ileum was associated with enhanced intestinal fibrosis and reduced let-7b expression by enrolling a prospective cohort of CD patients undergoing ileocolectomy. Besides, AIEC-infected IL-10-/- mice presented more severe intestinal fibrosis and could be improved by exogenous let-7b. Mechanistically, intestinal macrophages were found to be the main target of let-7b. Transferring let-7b-overexpressing macrophages to AIEC-infected IL-10-/- mice significantly alleviated intestinal fibrosis. In vitro, AIEC suppressed exosomal let-7b derived from intestinal epithelial cells (IECs), instead of the direct inhibition of let-7b in macrophages, to promote macrophages to a fibrotic phenotype. Finally, TGFßR1 was identified as one target of let-7b that regulates macrophage polarization. Overall, the results of our work indicate that AIEC is associated with enhanced intestinal fibrosis in CD. AIEC could inhibit exosomal let-7b from IECs to promote intestinal macrophages to a fibrotic phenotype and then contributed to fibrogenesis. Thus, anti-AIEC or let-7b therapy may serve as novel therapeutic approaches to ameliorate intestinal fibrosis.

What is the context?Adherent-invasive Escherichia coli (AIEC) plays an important role in the pathogenesis of Crohn's disease (CD) and has a strong association with intestinal fibrosis in animal models. However, how these bacteria contribute to intestinal fibrosis in CD patients is still unclear.The plasticity of macrophages is crucial in immune tolerance and tissue repair in the gastrointestinal tract, and the abnormal interaction between macrophages and gut bacteria triggers the fibrogenesis in the intestine.The association between the miRNA let-7b and fibrosis process has been widely reported in many tissues, except the intestine.What is new?AIEC colonization in the terminal ileum is associated with severe intestinal fibrosis in CD patients and the let-7b plays an anti-fibrotic role in intestinal fibrosis.Intestinal macrophages are the key modulator of AIEC-induced fibrosis and can be promoted to an antifibrotic phenotype through let-7b-targeted TGFßR1 inhibition.AIEC suppresses intestinal epithelial cell-derived exosomal let-7b to promote intestinal macrophages to a fibrotic phenotype, rather than a direct effect on macrophage regulation.What is the impact? Anti-AIEC and let-7b therapy may serve as potential therapeutic strategies to reduce intestinal fibrosis in CD in the future.

One-step self-assembly of multilayer graphene oxide via streamlined click reactions for sensitive colorimetric assays.

Hemin-loaded graphene oxide with excellent peroxidase-like activity shows great potential for biosensing applications. However, the detection sensitivity of biosensors based on such catalytic methods is limited by the lack of a signal amplification technique. In this work, we developed a simple and rapid signal amplification method based on streamlined click reactions enabling one-step assembly of multilayer graphene oxide nanosheets on magnetic beads to immobilize large amounts of hemin serving as active catalysts, which allowed for the highly sensitive detection of various biological targets, including copper ions, DNA sequences and proteins. With this method, we achieved detection limits down to 13.74 nM, 4.89 pM and 7.77 pg/mL for Cu2+, Ebola virus DNA sequences, and carcinoembryonic antigen, respectively. The designed platform holds great promise in the self-assembly of graphene-based nanozymes and sensitive colorimetric biosensing in a wider range of applications.

SbPHO2, a conserved Pi starvation signalling gene, is involved in the regulation of the uptake of multiple nutrients in sorghum.

Sorghum is one of the five most productive crops worldwide, but its yield is seriously limited by phosphate (Pi) availability. Although inorganic Pi signalling is well studied in Arabidopsis and rice, it remains largely unknown in sorghum. The sorghum sbpho2 mutant was identified, showing leaf necrosis and short roots. Map-based cloning identified SbPHO2 as Sobic.009G228100, an E2 conjugase gene that is a putative orthologue of the PHO2 genes in rice and Arabidopsis, which play important roles in Pi signalling. Pi starvation experiments and transformation of SbPHO2 into the rice ospho2 mutant further revealed that SbPHO2 is likely involved in Pi accumulation and root architecture alteration in sorghum. qRTPCR results showed that SbPHO2 was expressed in almost the entire plant, especially in the leaves. Furthermore, some typical Pi starvation-induced genes were induced in sbpho2 even under Pi-sufficient conditions, including Pi transporters, SPXs, phosphatases and lipid composition alteration-related genes. In addition to P accumulation in the shoots of sbpho2, concentrations of N, K, and other metal elements were also altered significantly in the sbpho2 plants. Nitrate uptake was also suppressed in the sbpho2 mutant. Consistent with this finding, the expression of several nitrate-, potassium- and other metal element-related genes was also altered in sbpho2. Furthermore, the results indicated that N-dependent control of the P starvation response is regulated via SbPHO2 in sorghum. Our results suggest that SbPHO2 participates in the regulation of the absorption of multiple nutrients, although PHO2 is a crucial and conserved component of Pi starvation signalling.

Molecular Evolutionary Growth of Ultralong Semiconducting Double-Walled Carbon Nanotubes.

The self-assembling preparation accompanied with template auto-catalysis loop and the ability to gather energy, induces the appearance of chirality and entropy reduction in biotic systems. However, an abiotic system with biotic characteristics is of great significance but still missing. Here, it is demonstrated that the molecular evolution is characteristic of ultralong carbon nanotube preparation, revealing the advantage of chiral assembly through template auto-catalysis growth, stepwise-enriched chirality distribution with decreasing entropy, and environmental effects on the evolutionary growth. Specifically, the defective and metallic nanotubes perform inferiority to semiconducting counterparts, among of which the ones with double walls and specific chirality (n, m) are more predominant due to molecular coevolution. An explicit evolutionary trend for tailoring certain layer chirality is presented toward perfect near-(2n, n)-containing semiconducting double-walled nanotubes. These findings extend our conceptual understanding for the template auto-catalysis assembly of abiotic carbon nanotubes, and provide an inspiration for preparing chiral materials with kinetic stability by evolutionary growth.

Controllable Preparation and Strengthening Strategies towards High-Strength Carbon Nanotube Fibers.

Carbon nanotubes (CNTs) with superior mechanical properties are expected to play a role in the next generation of critical engineering mechanical materials. Crucial advances have been made in CNTs, as it has been reported that the tensile strength of defect-free CNTs and carbon nanotube bundles can approach the theoretical limit. However, the tensile strength of macro carbon nanotube fibers (CNTFs) is far lower than the theoretical level. Although some reviews have summarized the development of such fiber materials, few of them have focused on the controllable preparation and performance optimization of high-strength CNTFs at different scales. Therefore, in this review, we will analyze the characteristics and latest challenges of multiscale CNTFs in preparation and strength optimization. First, the structure and preparation of CNTs are introduced. Then, the preparation methods and tensile strength characteristics of CNTFs at different scales are discussed. Based on the analysis of tensile fracture, we summarize some typical strategies for optimizing tensile performance around defect and tube-tube interaction control. Finally, we introduce some emerging applications for CNTFs in mechanics. This review aims to provide insights and prospects for the controllable preparation of CNTFs with ultra-high tensile strength for emerging cutting-edge applications.

Orally Administered Platinum Nanomarkers for Urinary Monitoring of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease with rising incidence worldwide. There is an increasing desire for non-invasive diagnostic tools to enable simple and sensitive IBD monitoring. Here, we report an orally administered nanosensor which will dissociate into ultrasmall platinum nanoclusters (PtNCs) in IBD-related inflammatory microenvironments. By exploiting the enzyme-mimicking activity of PtNCs and the precise bandpass filterability of kidney, the released-PtNCs can be detected in a scalable urinary readout, such as fluorescence and volumetric bar-chart chip (V-Chip), for point-of-care (POC) analysis. Our results demonstrate that the nanosensors exhibit significant signal differences between IBD-model mice and healthy mice, which is more sensitive than clinical ELISA assay based on fecal calprotectin. Such a non-invasive diagnostic modality significantly assists in the personalized assessment of pharmacological and follow-up efficacy. We envision that this modular conception will promote the rapid diagnosis of diverse diseases by changing specific responsive components.

Integrative network pharmacology and experimental verification to reveal the anti-inflammatory mechanism of ginsenoside Rh4.

Inflammation is an innate immune response to infection, and it is the main factor causing bodily injury and other complications in the pathological process. Ginsenoside Rh4 (G-Rh4), a minor ginsenoside of Panax ginseng C. A. Meyer and Panax notoginseng, has excellent pharmacological properties. However, many of its major pharmacological mechanisms, including anti-inflammatory actions, remain unrevealed. In this study, network pharmacology and an experimental approach were employed to elucidate the drug target and pathways of G-Rh4 in treating inflammation. The potential targets of G-Rh4 were selected from the multi-source databases, and 58 overlapping gene symbols related to G-Rh4 and inflammation were obtained for generating a protein-protein interaction (PPI) network. Molecular docking revealed the high affinities between key proteins and G-Rh4. Gene ontology (GO) and pathway enrichment analyses were used to analyze the screened core targets and explore the target-pathway networks. It was found that the JAK-STAT signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway may be the key and main pathways of G-Rh4 to treat inflammation. Additionally, the potential molecular mechanisms of G-Rh4 predicted from network pharmacology analysis were validated in RAW264.7 cells. RT-PCR, Western blot, and ELISA analysis indicated that G-Rh4 significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, as well as inflammation-related enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, in vitro experiments evaluated that Ginsenoside Rh4 exerts anti-inflammatory effects via the NF-κB and STAT3 signaling pathways. It is believed that our study will provide the basic scientific evidence that G-Rh4 has potential anti-inflammatory effects for further clinical studies.

Risk Factors for Worsening of Bone Loss in Patients Newly Diagnosed with Inflammatory Bowel Disease.

Background: Bone loss is common in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of metabolic bone disease in patients newly diagnosed with IBD and to identify the risk factors for bone loss over time. Methods: We performed a retrospective, both cross-sectional and longitudinal, study to extract the risk factors of bone loss (including osteopenia and osteoporosis) in patients newly diagnosed with IBD, using dual-energy X-ray absorptiometry (DXA). Results: A total of 639 patients newly diagnosed with IBD that had at least one DXA were included in the cross-sectional study. Osteopenia and osteoporosis were diagnosed in 24.6% and 5.4% of patients, respectively. Age at diagnosis, body mass index, and serum phosphorus were identified as independent factors associated with bone loss at baseline. A total of 380 of the 639 IBD patients (including 212 CD patients and 168 UC patients) with at least a second DXA scan were included in the longitudinal study. 42.6% of the patients presented a worsening of bone loss in the follow-up study. Menopause, albumin, and use of corticosteroids were identified as independent factors associated with worsening of bone loss. Conclusions: Metabolic bone disease is common in IBD patients, and there is a significant increase in prevalence of bone loss over time. Postmenopausal female, malnourished patients, and those requiring corticosteroid treatment are at risk for persistent bone loss. Therefore, BMD measurements and early intervention with supplementation of calcium and vitamin D are recommended in IBD patients with high-risk factors.

DPD Simulation on the Transformation and Stability of O/W and W/O Microemulsions.

The dissipative particle dynamics simulation method is adopted to investigate the microemulsion systems prepared with surfactant (H1T1), oil (O) and water (W), which are expressed by coarse-grained models. Two topologies of O/W and W/O microemulsions are simulated with various oil and water ratios. Inverse W/O microemulsion transform to O/W microemulsion by decreasing the ratio of oil-water from 3:1 to 1:3. The stability of O/W and W/O microemulsion is controlled by shear rate, inorganic salt and the temperature, and the corresponding results are analyzed by the translucent three-dimensional structure, the mean interfacial tension and end-to-end distance of H1T1. The results show that W/O microemulsion is more stable than O/W microemulsion to resist higher inorganic salt concentration, shear rate and temperature. This investigation provides a powerful tool to predict the structure and the stability of various microemulsion systems, which is of great importance to developing new multifunctional microemulsions for multiple applications.