Safety and efficacy of phage application in bacterial decolonisation:a systematic review

Colonisation by bacterial pathogens typically precedes invasive infection and seeds transmission. Thus, effective decolonisation strategies are urgently needed. The literature reports attempts to use phages for decolonisation. To assess the in-vivo efficacy and safety of phages for bacterial decolonisation, we performed a systematic review by identifying relevant studies to assess the in-vivo efficacy and safety of phages for bacterial decolonisation. We searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and the Cochrane Library to identify relevant articles published between Jan 1, 1990, and May 12, 2023, without language restrictions. We included studies that assessed the efficacy of phage for bacterial decolonisation in humans or vertebrate animal models. This systematic review is registered with PROSPERO, CRD42023457637. We identified 6694 articles, of which 56 (51 animal studies and five clinical reports) met the predetermined selection criteria and were included in the final analysis. The gastrointestinal tract (n=49, 88%) was the most studied bacterial colonisation site, and other sites were central venous catheters, lung, nose, skin, and urinary tract. Of the 56 included studies, the bacterial load at the colonisation site was reported to decrease significantly in 45 (80%) studies, but only five described eradication of the target bacteria. 15 studies reported the safety of phages for decolonisation. No obvious adverse events were reported in both the short-term and long-term observation period. Given the increasing life-threatening risks posed by bacteria that are difficult to treat, phages could be an alternative option for bacterial decolonisation, although further optimisation is required before their application to meet clinical needs.</p

Large vessel occlusion stroke outcomes in diabetic vs. non-diabetic patients with acute stress hyperglycemia

ObjectiveThis study assesses whether stress-induced hyperglycemia is a predictor of poor outcome at 3 months for patients with acute ischemic stroke (AIS) treated by endovascular treatment (EVT) and impacted by their previous blood glucose status.MethodsThis retrospective study collected data from 576 patients with AIS due to large vessel occlusion (LVO) treated by EVT from March 2019 to June 2022. The sample was composed of 230 and 346 patients with and without diabetes mellitus (DM), respectively, based on their premorbid diabetic status. Prognosis was assessed with modified Rankin Scale (mRS) at 3-month after AIS. Poor prognosis was defined as mRS&gt;2. Stress-induced hyperglycemia was assessed by fasting glucose-to-glycated hemoglobin ratio (GAR). Each group was stratified into four groups by quartiles of GAR (Q1–Q4). Binary logistic regression analysis was used to identify relationship between different GAR quartiles and clinical outcome after EVT.ResultsIn DM group, a poor prognosis was seen in 122 (53%) patients and GAR level was 1.27 ± 0.44. These variables were higher than non-DM group and the differences were statistically significant (p &lt; 0.05, respectively). Patients with severe stress-induced hyperglycemia demonstrated greater incidence of 3-month poor prognosis (DM: Q1, 39.7%; Q2, 45.6%; Q3, 58.6%; Q4, 68.4%; p = 0.009. Non-DM: Q1, 31%; Q2, 32.6%; Q3, 42.5%; Q4, 64%; p &lt; 0.001). However, the highest quartile of GAR was independently associated with poor prognosis at 3 months (OR 3.39, 95% CI 1.66–6.96, p = 0.001), compared to the lowest quartile in non-DM patients after logistic regression. This association was not observed from DM patients.ConclusionThe outcome of patients with acute LVO stroke treated with EVT appears to be influenced by premorbid diabetes status. However, the poor prognosis at 3-month in patients with DM is not independently correlated with stress-induced hyperglycemia. This could be due to the long-term damage of persistent hyperglycemia and diabetic patients’ adaptive response to stress following acute ischemic damage to the brain

Lymphoma endothelium preferentially expresses Tim-3 and facilitates the progression of lymphoma by mediating immune evasion

Angiogenesis is increasingly recognized as an important prognosticator associated with the progression of lymphoma and as an attractive target for novel modalities. We report a previously unrecognized mechanism by which lymphoma endothelium facilitates the growth and dissemination of lymphoma by interacting with circulated T cells and suppresses the activation of CD4+ T cells. Global gene expression profiles of microdissected endothelium from lymphoma and reactive lymph nodes revealed that T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) was preferentially expressed in lymphoma-derived endothelial cells (ECs). Clinically, the level of Tim-3 in B cell lymphoma endothelium was closely correlated to both dissemination and poor prognosis. In vitro, Tim-3+ ECs modulated T cell response to lymphoma surrogate antigens by suppressing activation of CD4+ T lymphocytes through the activation of the interleukin-6–STAT3 pathway, inhibiting Th1 polarization, and providing protective immunity. In a lymphoma mouse model, Tim-3–expressing ECs promoted the onset, growth, and dissemination of lymphoma by inhibiting activation of CD4+ T cells and Th1 polarization. Our findings strongly argue that the lymphoma endothelium is not only a vessel system but also a functional barrier facilitating the establishment of lymphoma immune tolerance. These findings highlight a novel molecular mechanism that is a potential target for enhancing the efficacy of tumor immunotherapy and controlling metastatic diseases

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Rapid Screening and Preparative Isolation of Antioxidants from Alpinia officinarum Hance Using HSCCC Coupled with DPPH-HPLC Assay and Evaluation of Their Antioxidant Activities

An efficient method using high-speed counter-current chromatography (HSCCC) coupled with DPPH-HPLC assay has been developed for rapid screening and preparative isolation of antioxidants from ethyl acetate fraction of Alpinia officinarum Hance. Target-guided by DPPH-HPLC assay, two antioxidants, galangin and kaempferide, were targeted and further separated with purities of 99.3% and 98.5% by HSCCC using petroleum ether–ethyl acetate–methanol–water (0.8 : 1 : 1 : 0.8, v/v) as the solvent system. The antioxidant activities of galangin and kaempferide were further evaluated by measuring their inhibiting effects on superoxide anion radical, hydroxyl radical, and hydrogen peroxide in different luminol chemiluminescence (CL) systems. As a result, galangin and kaempferide both showed potent antioxidant activities. Results of the present study indicated that the combinative method by offline coupling DPPH-HPLC and HSCCC could be widely applied for rapid screening and isolation of antioxidants from complex TCM extract

Isolation and purification of lignans from Schisandra chinensis by combination of silica gel column and high-speed counter-current chromatography

Silica gel column combined with high-speed counter-current chromatography separation was successfully applied to the separation of schizandrin (I), angeloylgomisin H (II), gomisin A (III), schisantherin C (IV), deoxyschizandrin (V), γ-schisandrin (VI) and schisandrin C (VII) from the fruits of Schisandra chinensis (Turcz.) Baillon. The petroleum ether extracts of the fruits of S. chinensis were pre-separated first on a silica gel column and divided into two fractions as sample 1 and sample 2. 260 mg of sample 1 was separated by HSCCC using petroleum ether-ethyl acetate-methanol-water (10:8:10:8, v/v) as the two-phase solvent system and 18.2 mg of schizandrin, 15.7 mg of angeloylgomisin H, 16.5 mg of gomisin A and 16.7 mg of schisantherin C were obtained. 230 mg of sample 2 was separated using petroleum ether-ethyl acetate-methanol-water (10:0.5:10:1, v/v) as the two-phase solvent system and 19.7 mg of deoxyschizandrin, 23.4 mg of γ-schisandrin and 18.2 mg of schisandrin C were obtained. The purities of the separated compounds were all over 94% as determined by HPLC. The chemical structures of these compounds were confirmed by ESI-MS and 1H NMR. [Acknowledgments. Natural Science Foundation of China (20872083), scientific and technological major special project (2010ZX09401-302-5-12) and the Key Science and Technology Program of Shandong Province (BS2009SW047)