SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma.

While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at lysine 22 (K22me3) on RPL40, a core ribosomal protein located in the GTPase activation center, was first reported 27 years ago. Yet, its methyltransferase and role in translation remain unexplored. Here, we report that SMYD5 has robust in vitro activity toward RPL40 K22 and primarily catalyzes RPL40 K22me3 in cells. The loss of SMYD5 and RPL40 K22me3 leads to reduced translation output and disturbed elongation as evidenced by increased ribosome collisions. SMYD5 and RPL40 K22me3 are upregulated in hepatocellular carcinoma (HCC) and negatively correlated with patient prognosis. Depleting SMYD5 renders HCC cells hypersensitive to mTOR inhibition in both 2D and 3D cultures. Additionally, the loss of SMYD5 markedly inhibits HCC development and growth in both genetically engineered mouse and patient-derived xenograft (PDX) models, with the inhibitory effect in the PDX model further enhanced by concurrent mTOR suppression. Our findings reveal a novel role of the SMYD5 and RPL40 K22me3 axis in translation elongation and highlight the therapeutic potential of targeting SMYD5 in HCC, particularly with concurrent mTOR inhibition. This work also conceptually broadens the understanding of lysine methylation, extending its significance from transcriptional regulation to translational control.

Porous red mud ceramsite for aquatic phosphorus removal: Application in constructed wetlands.

Red mud (RM) and spent oyster mushroom substrate (SOMS), by-products of industrial and agricultural production, can be recycled for polluted freshwater purification, bringing about a win-win situation. In this study, unacidified RM and RM acidified with oxalic acid (O-RM) and hydrochloric acid (H-RM), respectively, were mixed with SOMS to produce a porous ceramsite as a potential constructed wetlands (CWs) substrate. The results showed that the O-RM, H-RM, and RM ceramsites displayed fine compressive strengths of 7.75 ± 1.14, 8.40 ± 1.30, and 8.84 ± 0.69 MPa after calcining at 950 °C for 30 min, respectively. The phosphorus adsorption capacities of H-RM, O-RM, and RM ceramsite at a solid-liquid ratio of 25 g/L were 1.18 mg/g, 0.88 mg/g, and 1.06 mg/g, respectively. Toxicity release experiments showed that the ceramsites did not cause secondary environmental pollution, except for arsenic (ranging from 0.210 to 0.238 mg/L). The H-RM ceramsite was tested in a tidal flow-vertical flow CW (TF-VFCW) with Iris pseudacorus L. and Canna indica L plants. In the TF-VFCW, the average chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), total nitrogen (TN), and total phosphorus (TP) removal rates were 81.01, 90.25, 66.90, and 77.32 %, respectively. Plant growth had less impact on COD and NH4-N removal but had greater limited TN and TP removal. Scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis confirmed that acid pretreatment and the incorporation of SOMS significantly increased the surface and interior porous structures of the ceramsite and enhanced phosphate adsorption by the polyhydroxyl aluminum-iron complex ions. Bacteroides and Campylobacter used the energy produced during polyhydroxyalkanoic acid (PHA) catabolism to absorb phosphorus. Therefore, the synergistic effect of the substrate, plants, and microorganisms achieved the removal of phosphorus from CWs and offered effective and environmentally friendly recycling of RM and SOMS.

Design and Synthesis of 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid Derivatives as PP5 Inhibitors To Reverse Temozolomide Resistance in Glioblastoma Multiforme.

The serine/threonine phosphatase family is important in tumor progression and survival. Due to the high conserved catalytic domain, designing selective inhibitors is challenging. Herein, we obtained compound 28a with 38-fold enhanced PP5 selectivity (PP2A/5 IC50 = 33.8/0.9 µM) and improved drug-like properties (favorable stability and safety, F = 82.0%) by rational drug design based on a phase II PP2A/5 dual target inhibitor LB-100. Importantly, we found the spatial conformational restriction of the 28a indole fragment was responsible for the selectivity of PP5. Thus, 28a activated p53 and downregulated cyclin D1 and MGMT, which showed potency in cell cycle arrest and reverse temozolomide (TMZ) resistance in the U87 MG cell line. Furthermore, oral administration of 28a and TMZ was well tolerated to effectively inhibit tumor growth (TGI = 87.7%) in the xenograft model. Collectively, these results implicate 28a could be a drug candidate by reversing TMZ resistance with a selective PP5 inhibition manner.

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Shanxi Province holds an important strategic position in the overall ecological pattern of the Yellow River Basin. To investigate the changes of the ecological environment in the Shanxi section of the Yellow River Basin from 2000 to 2020, we selected MODIS remote sensing image data to determine the remote sensing ecological index (RSEI) based on the principal component analysis of greenness, humidity, dryness, and heat. Then, we analyzed the spatial and temporal variations of ecological quality in this region to explore the influencing factors. We further used the CA-Markov model to simulate and predict the ecological environment under different development scenarios in the Shanxi section of the Yellow River Basin in 2030. The results showed that RSEI had good applicability in the Shanxi section of the Yellow River Basin which could be used to monitor and evaluate the spatiotemporal variations in its ecological environment. From 2000 to 2020, the Shanxi section of the Yellow River Basin was dominated by low quality habitat areas, in which the ecological environment quality continued to improve from 2000 to 2010 and decreased from 2010 to 2020. The high quality habitat areas mainly located on the mountainous areas with superior natural conditions and rich biodiversity, while the low ecological quality areas were mainly in the Taiyuan Basin and the northern part of the study area, where the mining industry developed well. Climate factors were negatively correlated with ecological environment quality in the northern and central parts of the study area, and positively correlated with that in the mountainous area. Under all three development scenarios, the area of cultivated land, forest, water and construction land increased in 2030 compared to that in 2020. Compared to the natural development scenario and the cultivated land protection scenario, the ecological constraint scenario with RSEI as the limiting factor had the highest area of new forest and the lowest expansion rate of cultivated land and construction land. The results would provide a reference for land space planning and ecological environment protection in the Shanxi section of the Yellow River Basin.

Assessment of birth cohort screening of chronic hepatitis C in colorectal cancer screening patients in British Columbia.

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.

Radiotherapy-sensitized cancer immunotherapy via cGAS-STING immune pathway by activatable nanocascade reaction.

Radiotherapy-induced immune activation holds great promise for optimizing cancer treatment efficacy. Here, we describe a clinically used radiosensitizer hafnium oxide (HfO2) that was core coated with a MnO2 shell followed by a glucose oxidase (GOx) doping nanoplatform (HfO2@MnO2@GOx, HMG) to trigger ferroptosis adjuvant effects by glutathione depletion and reactive oxygen species production. This ferroptosis cascade potentiation further sensitized radiotherapy by enhancing DNA damage in 4T1 breast cancer tumor cells. The combination of HMG nanoparticles and radiotherapy effectively activated the damaged DNA and Mn2+-mediated cGAS-STING immune pathway in vitro and in vivo. This process had significant inhibitory effects on cancer progression and initiating an anticancer systemic immune response to prevent distant tumor recurrence and achieve long-lasting tumor suppression of both primary and distant tumors. Furthermore, the as-prepared HMG nanoparticles "turned on" spectral computed tomography (CT)/magnetic resonance dual-modality imaging signals, and demonstrated favorable contrast enhancement capabilities activated by under the GSH tumor microenvironment. This result highlighted the potential of nanoparticles as a theranostic nanoplatform for achieving molecular imaging guided tumor radiotherapy sensitization induced by synergistic immunotherapy.

A Novel Method of Synthesizing Polymeric Aluminum Ferric Sulfate Flocculant and Preparing Red Mud-Based Ceramsite.

A synthetic flocculant of aluminum (Al) and iron (Fe) extracted from red mud (RM) has been widely used in sewage treatment, while the remaining RM residue has been ignored. This study aimed to synthesize polymeric aluminum ferric sulfate (PAFS) flocculant from RM by acid leaching and then use the acidified RM residue to produce an acid RM-based ceramsite (ARMC) by mixing bentonite, hydroxypropyl methylcellulose, and starch. Our results showed that sintering, reaction temperature, H2SO4 concentration, reaction time, and liquid-to-solid ratio had an obvious effect on the leaching of Al and Fe in RM, which was a necessary prerequisite for the efficient PAFS flocculants. At a PAFS dosage of 60 mg/L, turbidity and phosphate removal rates were 95.21 ± 0.64% and 89.17 ± 0.52%, respectively. When the pH value was 8.0, the turbidity and phosphate removal efficiency were 99.22 ± 0.66% and 95.98 ± 1.63%, respectively. Considering the adsorption capacity and mechanical properties, the best conditions for ARMC production included using 60% ARM and ceramsite calcination at 600 °C, with the BET surface area 56.16 m2/g and a pore volume of 0.167 cm3/g. Thermogravimetric analysis indicated that 400 °C was a reasonable preheating temperature to enhance the ARMC mechanical strength, as this temperature allows the removal of surface-adsorbed and constituent water. Under a scanning electron microscope, the ARMC appeared rough before adsorption, while relatively uniform pores occupied it after adsorption. Our conclusion will help to improve the zero-waste strategy of RM and speed up the industrial production of RM in flocculants as well as utilizing ARMC as a new type of adsorbent for phosphorus adsorption in sewage treatment.

Novel reaction systems for catalytic synthesis of structured phospholipids.

Phospholipids are distinctive, adaptable molecules that are crucial to numerous biological systems. Additionally, their various architectures and amphiphilic characteristics support their unrivaled crucial functions in scientific and industrial applications. Due to their enormous potential for use in the fields of medicine, food, cosmetics, and health, structured phospholipids, which are modified phospholipids, have garnered increased attention. Traditional extraction methods, however, are pricy, resource-intensive, and low-yielding. The process of enzyme-catalyzed conversion is effective for producing several types of structured phospholipase. However, most frequently employed catalytic procedures involve biphasic systems with organic solvents, which have a relatively large mass transfer resistance and are susceptible to solvent residues and environmental effects due to the hydrophobic nature of phospholipids. Therefore, the adoption of innovative, successful, and environmentally friendly enzyme-catalyzed conversion systems provides a new development route in the field of structured phospholipids processing. Several innovative catalytic reaction systems are discussed in this mini-review, including aqueous-solid system, mixed micelle system, water-in-oil microemulsion system, Pickering emulsion system, novel solvent system, three-liquid-phase system, and supercritical carbon dioxide solvent system. However, there is still a glaring need for a thorough examination of these systems for the enzymatic synthesis of structural phospholipids. In terms of the materials utilized, applicability, benefits and drawbacks, and comparative effectiveness of each system, this research establishes further conditions for the system's selection. To create more effective biocatalytic processes, it is still important to build green biocatalytic processes with improved performance. KEY POINTS: • The latest catalytic systems of phospholipase D are thoroughly summarized. • The various systems are contrasted, and their traits are enumerated. • Different catalytic systems' areas of applicability and limitations are discussed.

Small molecules targeting molecular chaperones for tau regulation: Achievements and challenges.

Abnormal post-translational modification of microtubule-associated protein Tau (MAPT) is a prominent pathological feature in Alzheimer's disease (AD). Previous research has focused on designing small molecules to target Tau modification, aiming to restore microtubule stability and regulate Tau levels in vivo. However, progress has been hindered, and no effective Tau-targeted drugs have been successfully marketed, which urgently requires more strategies. Heat shock proteins (HSPs), especially Hsp90 and Hsp70, have been found to play a crucial role in Tau maturation and degradation. This review explores innovative approaches using small molecules that interact with the chaperone system to regulate Tau levels. We provide a comprehensive overview of the mechanisms involving HSPs and their co-chaperones in the Tau regulation cycle. Additionally, we analyze small molecules targeting these chaperone systems to modulate Tau function. By understanding the characteristics of the molecular chaperone system and its specific impact on Tau, we aim to provide a perspective that seeks to regulate Tau levels through the manipulation of the molecular chaperone system and ultimately develop effective treatments for AD.

Prolonged Exposure to High Glucose Induces Premature Senescence Through Oxidative Stress and Autophagy in Retinal Pigment Epithelial Cells.

Chronic hyperglycemia involves persistent high-glucose exposure and correlates with retinal degeneration. It causes various diseases, including diabetic retinopathy (DR), a major cause of adult vision loss. Most in vitro studies have investigated the damaging short-term effects of high glucose exposure on retinal pigment epithelial (RPE) cells. DR is also a severe complication of diabetes. In this study, we established a model with prolonged high-glucose exposure (15 and 75 mM exogenous glucose for two months) to mimic RPE tissue pathophysiology in patients with hyperglycemia. Prolonged high-glucose exposure attenuated glucose uptake and clonogenicity in ARPE-19 cells. It also significantly increased reactive oxygen species levels and decreased antioxidant protein (superoxide dismutase 2) levels in RPE cells, possibly causing oxidative stress and DNA damage and impairing proliferation. Western blotting showed that autophagic stress, endoplasmic reticulum stress, and genotoxic stress were induced by prolonged high-glucose exposure in RPE cells. Despite a moderate apoptotic cell population detected using the Annexin V-staining assay, the increases in the senescence-associated proteins p53 and p21 and SA-ß-gal-positive cells suggest that prolonged high-glucose exposure dominantly sensitized RPE cells to premature senescence. Comprehensive next-generation sequencing suggested that upregulation of oxidative stress and DNA damage-associated pathways contributed to stress-induced premature senescence of ARPE-19 cells. Our findings elucidate the pathophysiology of hyperglycemia-associated retinal diseases and should benefit the future development of preventive drugs. Prolonged high-glucose exposure downregulates glucose uptake and oxidative stress by increasing reactive oxygen species (ROS) production through regulation of superoxide dismutase 2 (SOD2) expression. Autophagic stress, ER stress, and DNA damage stress (genotoxic stress) are also induced by prolonged high-glucose exposure in RPE cells. Consequently, multiple stresses induce the upregulation of the senescence-associated proteins p53 and p21. Although both apoptosis and premature senescence contribute to high glucose exposure-induced anti-proliferation of RPE cells, the present work shows that premature senescence rather than apoptosis is the dominant cause of RPE degeneration, eventually leading to the pathogenesis of DR.

TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis.

TERT reactivation occurs frequently in human malignancies, especially advanced cancers. However, in vivo functions of TERT reactivation in cancer progression and the underlying mechanism are not fully understood. In this study, we expressed TERT and/or active BRAF (BRAF V600E) specifically in mouse thyroid epithelium. While BRAF V600E alone induced papillary thyroid cancer (PTC), coexpression of BRAF V600E and TERT resulted in poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome analysis revealed that tumors from mice coexpressing BRAF V600E and TERT were highly heterogeneous, and cell dedifferentiation was positively correlated with ribosomal biogenesis. Mechanistically, TERT boosted ribosomal RNA (rRNA) expression and protein synthesis by interacting with multiple proteins involved in ribosomal biogenesis. Furthermore, we found that CX-5461, an rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation of thyroid cancer. Thus, TERT promotes thyroid cancer progression by inducing cancer cell dedifferentiation, and ribosome inhibition represents a potential strategy to treat TERT-reactivated cancers.

Optimization method to reduce the risky driving behaviors of ride-hailing drivers.

INTRODUCTION: To promote the safety level of ride-hailing services, this study develops the Targeted and Differentiated Optimization Method of Risky Driving Behavior Education and Training (TDOM-RDBET) founded on driver type classification of high-risk drivers. METHOD: Based on value and goal orientations, 689 drivers were classified into four driver types and were assigned to three groups, including an experimental group, a blank control group, and a general control group. This research preliminarily analyzes the effectiveness of the TDOM-RDBET to reduce mobile phone use while driving by assessing the main effects of the group and test session on the risk value ranking of mobile phone use while driving (AR), the frequency per 100 km of mobile phone use while driving (AF), and the frequency per 100 km of risky driving behaviors (AFR), as well as the interactive effects of the two factors on AR, AF, and AFR, based on a two-way analysis of variance (two-way ANOVA). RESULTS: The results demonstrate an overall significant reduction in AR (F = 8.653, p = 0.003), AF (F = 11.027, p = 0.001), and AFR (F = 8.072, p = 0.005) for the experimental group after training. Moreover, significant interactive effects of the driver group × test session on AR (F = 7.481, p = 0.001) and AF (F = 15.217, p < 0.001) were found. AR was significantly lower for the experimental group than for the blank control group (p < 0.05) in the post-training condition. Moreover, AF was also significantly lower for the experimental group than for the blank control group (p < 0.05) and general control group (p < 0.05) in the post-training condition. PRACTICAL APPLICATIONS: On the whole, it was preliminarily verified that the TDOM-RDBET is more effective than the general training method at modifying the risky driving behavior.

Allosteric autoregulation of DNA binding via a DNA-mimicking protein domain: a biophysical study of ZNF410-DNA interaction using small angle X-ray scattering.

ZNF410 is a highly-conserved transcription factor, remarkable in that it recognizes a 15-base pair DNA element but has just a single responsive target gene in mammalian erythroid cells. ZNF410 includes a tandem array of five zinc-fingers (ZFs), surrounded by uncharacterized N- and C-terminal regions. Unexpectedly, full-length ZNF410 has reduced DNA binding affinity, compared to that of the isolated DNA binding ZF array, both in vitro and in cells. AlphaFold predicts a partially-folded N-terminal subdomain that includes a 30-residue long helix, preceded by a hairpin loop rich in acidic (aspartate/glutamate) and serine/threonine residues. This hairpin loop is predicted by AlphaFold to lie against the DNA binding interface of the ZF array. In solution, ZNF410 is a monomer and binds to DNA with 1:1 stoichiometry. Surprisingly, the single best-fit model for the experimental small angle X-ray scattering profile, in the absence of DNA, is the original AlphaFold model with the N-terminal long-helix and the hairpin loop occupying the ZF DNA binding surface. For DNA binding, the hairpin loop presumably must be displaced. After combining biophysical, biochemical, bioinformatic and artificial intelligence-based AlphaFold analyses, we suggest that the hairpin loop mimics the structure and electrostatics of DNA, and provides an additional mechanism, supplementary to sequence specificity, of regulating ZNF410 DNA binding.

Retinal protective effect of curcumin metabolite hexahydrocurcumin against blue light-induced RPE damage.

BACKGROUND: Age-related macular degeneration (AMD) is a disease of retinal pigment epithelium (RPE) cells. We have previously demonstrated that blue light can damage RPE cells and their underlying mechanisms. We found that hexahydrocurcumin (HHC), a metabolite of curcumin, had better retinal protection than curcumin. However, the involved mechanisms remain unclear. METHODS: By exposing ARPE-19 human RPE cells and mouse primary RPE cells to blue light, the intracellular mechanisms of HHC in cells were investigated, including the proliferation of RPE cells and the effects of HHC on activating intracellular protective mechanisms and related factors. Next-generation sequencing (NGS) RNA sequencing revealed the underlying mechanisms involved in the induction and regulation of HHC treatment following blue light exposure. RESULTS: HHC promoted autophagy by enhancing autophagic flux, reduced oxidative stress and endoplasmic reticulum (ER) stress, and effectively reversed blue light-induced cell death. RNA sequencing-based bioinformatics approaches comprehensively analyze HHC-mediated cellular processes. CONCLUSION: Our findings elucidate the mechanisms of HHC against blue light damage in RPE cells and are beneficial for the development of natural metabolite-based preventive drugs or functional foods.

Activation of Pancreatic Acinar FXR Protects against Pancreatitis via Osgin1-Mediated Restoration of Efficient Autophagy.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

Transmembrane protein KIRREL1 regulates Hippo signaling via a feedback loop and represents a therapeutic target in YAP/TAZ-active cancers.

The Hippo tumor-suppressor pathway is frequently dysregulated in human cancers and represents a therapeutic target. However, strategies targeting the mammalian Hippo pathway are limited because of the lack of a well-established cell-surface regulator. Here, we show that transmembrane protein KIRREL1, by interacting with both SAV1 and LATS1/2, promotes LATS1/2 activation by MST1/2 (Hippo kinases), and LATS1/2 activation, in turn, inhibits activity of YAP/TAZ oncoproteins. Conversely, YAP/TAZ directly induce the expression of KIRREL1 in a TEAD1-4-dependent manner. Indeed, KIRREL1 expression positively correlates with canonical YAP/TAZ target gene expression in clinical tumor specimens and predicts poor prognosis. Moreover, transgenic expression of KIRREL1 effectively blocks tumorigenesis in a mouse intrahepatic cholangiocarcinoma model, indicating a tumor-suppressor role of KIRREL1. Hence, KIRREL1 constitutes a negative feedback mechanism regulating the Hippo pathway and serves as a cell-surface marker and potential drug target in cancers with YAP/TAZ dependency.

The Value of m5C-Related lncRNAs in the Prognostic Assessment and Immunotherapy of Stomach Adenocarcinoma.

Long noncoding RNAs (lncRNAs) are closely associated with a variety of tumors, including stomach adenocarcinoma (STAD). However, the role of 5-methylcytosine- (m5C-) related lncRNAs in STAD is still uncertain. This study investigated the value of m5C-related lncRNAs in prognostic evaluation and immunotherapy of STAD. STAD transcriptome sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database, and m5C-related lncRNAs were screened by Pearson correlation analysis. A prognostic m5C-related lncRNA signature (m5CRLSig) associated with STAD was established using univariate and multivariate Cox regression analysis. We constructed a prognostic risk model for STAD with six m5C-related lncRNAs. The receiver operating characteristic (ROC) curve was used to examine the predictive efficacy. Univariate and multifactorial Cox regression analysis and principal component analysis (PCA) validated m5CRLSig as an independent factor of STAD prognosis. The clinicopathological characteristics of the model showed higher risk scores for stages II-IV, grade 3, N1-3, and death status. The calibration curve of a nomogram revealed that the nomogram had an excellent predictive function for survival risk. Furthermore, the expression of six m5C-related lncRNAs in STAD and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR), which verified the feasibility of the m5CRLSig as a prognostic marker for STAD. m5C-related lncRNAs were linked to multiple immune-associated pathways, according to gene set enrichment analysis (GSEA). CIBERSORT analysis indicated that m5CRLSig was involved in immune cell infiltration. Risk score was associated with immune checkpoint gene expression, immune function scores, and chemotherapeutic drug sensitivity. Therefore, m5CRLSig can efficiently assess the prognosis of STAD patients and can be used as a biological marker for immunotherapy.

Effect of Probiotic-Assisted Eradication of cagA+/vacA s1m1 Helicobacter pylori on Intestinal Flora.

Objective: We attempted to evaluate the effects of probiotic-assisted eradication of cytotoxin-associated gene A (cagA)+/vacuolating cytotoxin A (vacA) s1m1 Helicobacter pylori (H. pylori) on the intestinal flora, inflammatory factors, and clinical outcomes. Methods: A total of 180 patients with cagA+/vacA s1m1 H. pylori were randomly divided into two groups. Group A was treated with bismuth quadruple therapy (BQT). Group B was treated with S. boulardii in addition to BQT. The distribution of intestinal flora, serum interleukin-8 (IL-8), IL-17, tumor necrosis factor-α (TNF-α) levels, recovery time of clinical symptoms, total effective rate of clinical symptoms, H. pylori eradication rate, and adverse reactions were observed. Results: 2 weeks after treatment, the contents of Bifidobacterium, Bacteroides, and Lactobacillus in the intestinal tract of Group A decreased, while the amounts of Enterococcus and Enterobacter increased. In Group B, the contents of Bifidobacterium, Bacteroides, and Lactobacillus increased, while the amounts of Enterococcus and Enterobacter did not change significantly. Moreover, the trend of this flora change was still present at 4 weeks after treatment. Compared with Group A, Group B had lower IL-8, IL-17, and TNF-α levels, shorter recovery time of clinical symptoms, higher overall efficiency of clinical symptoms, and lower occurrence of adverse reactions. The eradication rate did not differ significantly between the two groups. Conclusion: BQT can lead to intestinal flora disorders in cagA+/vacA s1m1 H. pylori patients. S. boulardii can improve the distribution of intestinal flora, downregulate immune-inflammatory mediators, and modify clinical symptoms in patients.

Reinvestigating FeBr3-Catalyzed Alcohol Oxidation with H2O2: Is a High-Valent Iron Species (HIS) or a Reactive Brominating Species (RBS) Responsible for Alcohol Oxidation?

In 2003, Martín et al. reported a green alcohol oxidation with FeBr3(cat.)/H2O2 and proposed a high-valent iron species (HIS) responsible for the alcohol oxidation. Reinvestigating this FeBr3(cat.)/H2O2 method led us to propose a different mechanism that involves a reactive brominating species (RBS) for the oxidation of alcohols. The evidence to support this RBS-based mechanism includes (1) our recent findings of in situ-generated RBS from the related FeBr2/H2O2 or CeBr3/H2O2 systems, (2) our results of a series of controlled experiments, and (3) some related RBS-based precedents (NBS, NBA, or Br2) showing similar high oxidation selectivity of secondary over primary alcohols. These studies enable us to discover that a RBS from CeBr3/H2O2 is much more efficient for the oxidation of secondary and benzylic alcohols, which represents a new green protocol for selective oxidation of alcohols to carbonyls.

Compositional Analysis of Four Kinds of Citrus Fruits with an NMR-Based Method for Understanding Nutritional Value and Rational Utilization: From Pericarp to Juice.

Citrus is one of the most important economic crops and is widely distributed across the monsoon region. Citrus fruits are deeply loved by consumers because of their special color, fragrance and high nutritional value. However, their health benefits have not been fully understood, especially the pericarps of citrus fruits which have barely been utilized due to their unknown chemical composition. In the present study, the pericarp and juices of four typical varieties of citrus fruits (lemon, dekopon, sweet orange and pomelo) were analyzed by NMR spectroscopy combined with pattern recognition. A total of 62 components from the citrus juices and 87 components from the citrus pericarps were identified and quantified, respectively. The different varieties of the citrus fruits could be distinguished from the others, and the chemical markers in each citrus juice and pericarp were identified by a combination of univariate and multivariate statistical analyses. The nutritional analysis of citrus juices offers favorable diet recommendations for human consumption and data guidance for their potential medical use, and the nutritional analysis of citrus pericarps provides a data reference for the subsequent comprehensive utilization of citrus fruits. Our results not only provide an important reference for the potential nutritional and medical values of citrus fruits but also provide a feasible platform for the traceability analysis, adulteration identification and chemical composition analysis of other fruits.