AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes.

Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

Toxic gas sensing performance of arsenene functionalized by single atoms (Ag, Au): a DFT study.

The detection and removal of toxic gases from the air are imminent tasks owing to their hazards to the environment and human health. Based on DFT calculations with VdW correction, adsorption configurations, adsorption energies, and electronic properties were compared for the adsorption of toxic gas molecules (CO, NO, NO2, SO2, NH3 and H2S) on pure arsenene (p-arsenene) and Ag/Au-doped arsenene (Ag/Au-arsenene). Our calculations show that all molecules considered to chemisorb on Ag/Au-arsenene and the substitution of noble metal, particularly Ag, could remarkably enhance the interactions and charge transfer between the gas molecules and Ag/Au-arsenene. Thus, Ag/Au-arsenene is expected to show higher sensitivity in detecting CO, NO, NO2, SO2, NH3 and H2S molecules than p-arsenene. Furthermore, the changes in the vibrational frequencies of gas molecules and the work functions of Ag/Au-arsenene substrates upon adsorption are shown to be closely related to the adsorption energies and charge transfer between the molecules and Ag/Au-arsenene, which is dependent on the molecules. Therefore, Ag/Au-arsenene-based gas sensors are expected to show good selectivity of molecules. The analysis of theoretical recovery time suggested that Ag-arsenene shows high reusability while detecting H2S, CO, and NO, whereas Au-arsenene has high selectivity to sensing NO at room temperature. With the increase in work temperature and decrease in recovery times, Ag/Au-arsenene could be used to detect NH3 and NO2 from factory emission and automobile exhaust with quite good reusability. The above results indicated that Ag/Au-arsenene shows good performance in toxic gas sensing with high sensitivity, selectivity, and reusability at different temperatures.

Pectin-based double network hydrogels as local depots of celastrol for enhanced antitumor therapy.

In this study, A double-network (DN) hydrogel composed of a physical glycyrrhizic acid (GA) network and a chemically crosslinked pectin-based network was fabricated as a local depot of celastrol (CEL) for cancer treatment. The obtained DN hydrogel possessed excellent mechanical performance, flexibility, biocompatibility, biodegradability and self-healing property. Furthermore, the release profile of CEL loaded DN hydrogel maintained a controlled and sustained release of CEL for a prolonged period. Finally, in vivo animal experiments demonstrated that the DN hydrogel could significantly enhance the therapeutic efficiency of CEL in CT-26 tumor-bearing mice upon intratumoral injection while effectively alleviate the toxicity of the CEL. In summary, this injectable pectin-based double network hydrogels are ideal delivery vehicle for tumor therapy.

Dietary Lactobacillus rhamnosus GG extracellular vesicles enhance antiprogrammed cell death 1 (anti-PD-1) immunotherapy efficacy against colorectal cancer.

There is a need to explore combination therapy to improve the efficacy of immunotherapy for colorectal cancer through food probiotics. In this study, extracellular vesicles (EV) derived from Lactobacillus rhamnosus GG (LGG-EV) were successfully isolated. Adjusting the culture temperature to 30 °C led to an elevated LGG-EV yield, and the addition of penicillin resulted in a decrease in particle size. In addition, LGG-EV have better gastrointestinal tract stability in a Ca2+ environment in vivo and in vitro. Oral administration of LGG-EV synergistically improved anti-PD-1 immunotherapy efficacy against colorectal cancer. Mechanistically, LGG-EV modulated intestinal immunity by increasing the CD8+ T/CD4+ T cell ratio in mesenteric lymph nodes and enhancing the ratio of MHC II+ DC cells, CD4+ T cells, and CD8+ T cells in tumor tissues. Meanwhile, the diversity of the gut microbiota and the abundance of beneficial bacteria, such as Lactobacillus, increased in the combined-treatment mice. In addition, there were significant changes in the levels of serum metabolites associated with the microbiota and anti-tumor effects, including uridine, which was elevated by the combination of anti-PD-1 and LGG-EV treatment. Our findings provide theoretical and mechanistic insights into the development of LGG-EV as postbiotics in combination with immune checkpoint inhibitors for cancer therapy.

Identification of urinary extracellular vesicles differentially expressed RNAs in diabetic nephropathy via whole-transcriptome integrated analysis.

BACKGROUND: Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes and a leading cause of chronic kidney disease worldwide. Urinary extracellular vesicles (uEVs), which are natural nanoscale vesicles that protect RNA from degradation, have the potential to serve as an invasive diagnostic biomarker for DN. METHODS: We enrolled 24 participants, including twelve with renal biopsy-proven T2DN and twelve with T2DM, and isolated uEVs using ultracentrifugation. We performed microarrays for mRNAs, lncRNAs, and circRNAs in parallel, and Next-Generation Sequencing for miRNAs. Differentially expressed RNAs (DE-RNAs) were subjected to CIBERSORTx, ssGSEA analysis, GO enrichment, PPI network analysis, and construction of the lncRNA/circRNA-miRNA-mRNA regulatory network. Candidate genes and potential biomarker RNAs were validated using databases and machine learning models. RESULTS: A total of 1684 mRNAs, 126 lncRNAs, 123 circRNAs and 66 miRNAs were found in uEVs in T2DN samples compared with T2DM. CIBERSORTx revealed the involvement of uEVs in immune activity and ssGSEA explored possible cell or tissue sources of uEVs. A ceRNA co-expression and regulation relationship network was constructed. Candidate genes MYO1C and SP100 mRNA were confirmed to be expressed in the kidney using Nephroseq database, scRNA-seq dataset, and Human Protein Atlas database. We further selected 2 circRNAs, 2 miRNAs, and 2 lncRNAs from WGCNAs and ceRNAs and demonstrated their efficacy as potential diagnostic biomarkers for T2DN using machine learning algorithms. CONCLUSIONS: This study reported, for the first time, the whole-transcriptome genetic resources found in urine extracellular vesicles of T2DN patients. The results provide additional support for the possible interactions, and regulators between RNAs from uEVs themselves and as potential biomarkers in DN.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Identifying immune infiltration by deep learning to assess the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: The treatment situation for hepatocellular carcinoma remains critical. The use of deep learning algorithms to assess immune infiltration is a promising new diagnostic tool. METHODS: Patient data and whole slide images (WSIs) were obtained for the Xijing Hospital (XJH) cohort and TCGA cohort. We wrote programs using Visual studio 2022 with C# language to segment the WSI into tiles. Pathologists classified the tiles and later trained deep learning models using the ResNet 101V2 network via ML.NET with the TensorFlow framework. Model performance was evaluated using AccuracyMicro versus AccuracyMacro. Model performance was examined using ROC curves versus PR curves. The percentage of immune infiltration was calculated using the R package survminer to calculate the intergroup cutoff, and the Kaplan‒Meier method was used to plot the overall survival curve of patients. Cox regression was used to determine whether the percentage of immune infiltration was an independent risk factor for prognosis. A nomogram was constructed, and its accuracy was verified using time-dependent ROC curves with calibration curves. The CIBERSORT algorithm was used to assess immune infiltration between groups. Gene Ontology was used to explore the pathways of differentially expressed genes. RESULTS: There were 100 WSIs and 165,293 tiles in the training set. The final deep learning models had an AccuracyMicro of 97.46% and an AccuracyMacro of 82.28%. The AUCs of the ROC curves on both the training and validation sets exceeded 0.95. The areas under the classification PR curves exceeded 0.85, except that of the TLS on the validation set, which might have had poor results (0.713) due to too few samples. There was a significant difference in OS between the TIL classification groups (p < 0.001), while there was no significant difference in OS between the TLS groups (p = 0.294). Cox regression showed that TIL percentage was an independent risk factor for prognosis in HCC patients (p = 0.015). The AUCs according to the nomogram were 0.714, 0.690, and 0.676 for the 1-year, 2-year, and 5-year AUCs in the TCGA cohort and 0.756, 0.797, and 0.883 in the XJH cohort, respectively. There were significant differences in the levels of infiltration of seven immune cell types between the two groups of samples, and gene ontology showed that the differentially expressed genes between the groups were immune related. Their expression levels of PD-1 and CTLA4 were also significantly different. CONCLUSION: We constructed and tested a deep learning model that evaluates the immune infiltration of liver cancer tissue in HCC patients. Our findings demonstrate the value of the model in assessing patient prognosis, immune infiltration and immune checkpoint expression levels.

Integrated analysis of RNA methylation regulators crosstalk and immune infiltration for predictive and personalized therapy of diabetic nephropathy.

BACKGROUND: RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. METHODS: The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. RESULTS: We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. CONCLUSION: Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.

Effect of granular activated carbon adsorption and size of microbial aggregates in inoculum on stimulating direct interspecies electron transfer during anaerobic digestion of fat, oil, and grease.

To investigate the effect of granular activated carbon (GAC) adsorption and size of microbial aggregates in inoculum on stimulating direct interspecies electron transfer (DIET) during anaerobic digestion of fat, oil, and grease (FOG), seed sludge was divided into two inocula (big (>0.85 mm)/small (0.15-0.85 mm)) for FOG digestion with/without GAC. More long-chain fatty acids (LCFAs) were adsorbed on GAC in the reactor with small aggregates than that with big aggregates, corresponding to 57 % and 10 % decreased methane production, respectively. Adsorption of unsaturated LCFAs (e.g., oleic acid) on GAC was found to reduce LCFA bioavailability, hinder DIET via GAC, and change community structure. Compared to pre-adsorption of oleic acid on GAC, pre-attachment of microbes on GAC resulted in 5.6-fold higher methane yield for oleic acid digestion. Together, competition of LCFA adsorption between GAC and microbial aggregates is essential for enhanced methane recovery from FOG digestion via GAC-induced DIET.

PRSS2 overexpression relates to poor prognosis and promotes proliferation, migration and invasion in gastric cancer.

Serine protease 2 (PRSS2) plays a pivotal role in tum or pathogenesis as a serine protease. In this paper, we investigated the expression and role of PRSS2 in gastric cancer (GC). Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry (IHC) were performed to detect PRSS2 expression in GC tissues. The correlations between PRSS2 and clinicopathological variables and prognosis were analyzed. The effects of PRSS2 on gastric cancer in vitro and in vivo were detected by Cell Counting Kit-8 (CCK-8), colony formation assay, migration and invasion test, and nude mouse experiment. We observed that the PRSS2 mRNA and protein levels were upregulated in GC tissues, and PRSS2 expression was associated with GC N stage. Patients with high PRSS2 expression have a poor prognosis. Finally, the regulatory effect of PRSS2 on the biological behaviors of GC cells was assessed in GC cells transfected with lentiviral interference fragments of PRSS2. The results suggested that PRSS2 knockdown decreased the proliferation, migration and invasion of GC cells and downregulated MMP-9 expression. In summary, PRSS2 overexpression is associated with poor postoperative prognosis in GC patients and can be used as a potential biomarker to assess the prognosis of GC.

Enhanced cadmium phytoremediation capacity of poplar is associated with increased biomass and Cd accumulation under nitrogen deposition conditions.

Nitrogen (N) deposition plays a significant role in soil cadmium (Cd) phytoremediation, and poplar has been considered for the remediation of contaminated soil because of its enormous biomass and strong Cd resistance. To reveal the underlying physiological and root phenotypic mechanisms of N deposition affecting Cd phytoextraction in poplar, we assessed root phenotypic characteristics, Cd absorption and translocation, chlorophyll fluorescence performance, and antioxidant enzyme activities of a clone of Populus deltoides × P. nigra through combined greenhouse Cd and N experiments. Our results showed that Cd significantly changed the root phenotype by reducing root length, tip number, and diameter. Cd also caused the peroxidation of lipids, damaged the photosystem II (PSII) reaction centre, and reduced photosynthetic capacity, resulting in a decrease in biomass accumulation in poplar. The N60 (60 kg N·ha-1·yr-1) and N90 (90 kg N·ha-1·yr-1) treatments promoted the net photosynthetic rate of poplar by increasing the activity of antioxidant enzymes and proline content and repairing the PSII reaction centre, thus increasing the biomass accumulation of poplar exposed to Cd stress. Simultaneously, the N60 and N90 treatments might have increased Cd uptake from the soil by upregulating total root length, root tips, and fine root length. Cd mainly accumulated in roots and stems but not in leaves. The N30 (30 kg N·ha-1·yr-1) treatment had no obvious effects on these parameters compared with the single Cd treatment. Consequently, our study suggested that adequate N can improve biomass and Cd accumulation to enhance the phytoremediation capacity of poplar for Cd, which might be related to the improvement of leaf physiological defence and the change in root phenotypic characteristics.

Creation of cotton mutant library based on linear electron accelerator radiation mutation.

Cotton (Gossypium spp.) is one of the most important cash crops worldwide. At present, new cotton varieties are mainly produced through conventional cross breeding, which is limited by available germplasm. Although the genome of cotton has been fully sequenced, research on the function of specific genes lags behind due to the lack of sufficient genetic material. Therefore, it is very important to create a cotton mutant library to create new, higher-quality varieties and identify genes associated with the regulation of key traits. Traditional mutagenic strategies, such as physical, chemical, and site-directed mutagenesis, are relatively costly, inefficient, and difficult to perform. In this study, we used a radiation mutation method based on linear electron acceleration to mutate cotton variety 'TM-1', for which a whole-genome sequence has previously been performed, to create a high throughput cotton mutant library. Abundant phenotypic variation was observed in the progeny population for three consecutive generations, including cotton fiber color variation, plant dwarfing, significant improvement of yield traits, and increased sensitivity to Verticillium wilt. These results show that radiation mutagenesis is an effective and feasible method to create plant mutant libraries.

Circulating tumor DNA: a noninvasive biomarker for tracking ovarian cancer.

Ovarian cancer is the fifth leading cause of cancer-related mortality in women worldwide. Despite the development of technologies over decades to improve the diagnosis and treatment of patients with ovarian cancer, the survival rate remains dismal, mainly because most patients are diagnosed at a late stage. Traditional treatment methods and biomarkers such as cancer antigen-125 as a cancer screening tool lack specificity and cannot offer personalized combinatorial therapy schemes. Circulating tumor DNA (ctDNA) is a promising biomarker for ovarian cancer and can be detected using a noninvasive liquid biopsy. A wide variety of ctDNA applications are being elucidated in multiple studies for tracking ovarian carcinoma during diagnostic and prognostic evaluations of patients and are being integrated into clinical trials to evaluate the disease. Furthermore, ctDNA analysis may be used in combination with multiple "omic" techniques to analyze proteins, epigenetics, RNA, nucleosomes, exosomes, and associated immune markers to promote early detection. However, several technical and biological hurdles impede the application of ctDNA analysis. Certain intrinsic features of ctDNA that may enhance its utility as a biomarker are problematic for its detection, including ctDNA lengths, copy number variations, and methylation. Before the development of ctDNA assays for integration in the clinic, such issues are required to be resolved since these assays have substantial potential as a test for cancer screening. This review focuses on studies concerning the potential clinical applications of ctDNA in ovarian cancer diagnosis and discusses our perspective on the clinical research aimed to treat this daunting form of cancer.

Radiation Effects in the Crystalline-Amorphous SiOC Polymer-Derived Ceramics: Insights from Experiments and Molecular Dynamics Simulation.

Radiation-tolerant materials are in great demand for safe operation and advancement of nuclear and aerospace systems. Nanostructuring is a key strategy to improve the radiation tolerance of materials. SiOC polymer-derived ceramics (PDCs) are unique synthetic nanocomposites consisting of ß-SiC nanocrystals and turbostratic graphite distributed in amorphous SiOC matrix, which are "all-rounder" materials for many advanced structural and functional applications. Radiation effects in the crystalline-amorphous system have been investigated in detail by experiments and molecular dynamics (MD) simulations. The results indicate that the amorphous SiOC structure retains amorphous accompanied by redistribution of the Si-containing tetrahedra. The graphite is shown to amorphize more easily than ß-SiC nanocrystals under the same irradiation condition. The sample richer in oxygen, namely, containing more amorphous SiOC, shows less disordering of graphite, resulting from greater mitigation of radiation damage by the amorphous phase as efficient sinks. This study provides details of the microstructure evolution of SiOC PDCs under ion irradiation, as well as insights for the design and development of advanced ion damage-resistant materials.

HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis.

Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.

"Metaphilic" Cell-Penetrating Polypeptide-Vancomycin Conjugate Efficiently Eradicates Intracellular Bacteria via a Dual Mechanism.

Infections by intracellular pathogens are difficult to treat because of the poor accessibility of antibiotics to the pathogens encased by host cell membranes. As such, a strategy that can improve the membrane permeability of antibiotics would significantly increase their efficiency against the intracellular pathogens. Here, we report the design of an adaptive, metaphilic cell-penetrating polypeptide (CPP)-antibiotic conjugate (VPP-G) that can effectively eradicate the intracellular bacteria both in vitro and in vivo. VPP-G was synthesized by attaching vancomycin to a highly membrane-penetrative guanidinium-functionalized metaphilic CPP. VPP-G effectively kills not only extracellular but also far more challenging intracellular pathogens, such as S. aureus, methicillin-resistant S. aureus, and vancomycin-resistant Enterococci. VPP-G enters the host cell via a unique metaphilic membrane penetration mechanism and kills intracellular bacteria through disruption of both cell wall biosynthesis and membrane integrity. This dual antimicrobial mechanism of VPP-G prevents bacteria from developing drug resistance and could also potentially kill dormant intracellular bacteria. VPP-G effectively eradicates MRSA in vivo, significantly outperforming vancomycin, which represents one of the most effective intracellular antibacterial agents reported so far. This strategy can be easily adapted to develop other conjugates against different intracellular pathogens by attaching different antibiotics to these highly membrane-penetrative metaphilic CPPs.

Serum SYPL1 is a promising diagnostic biomarker for colorectal cancer.

BACKGROUND: At present, the overall sensitivity and specificity of blood biomarkers are insufficient for a diagnosis of colorectal cancer (CRC). METHODS: We analyzed the serum synaptophysin like 1 (sSYPL1) in controls, adenoma patients, CRC patients, pre- and postoperative CRC patients by ELISA. RESULTS: The upregulation of SYPL1 was confirmed in CRC tissues at both mRNA and protein levels. Consistently, sSYPL1 was significantly higher in CRC patients than in either controls (t = 14.50, P < 0.0001) or adenoma patients (t = 10.56, P < 0.0001) and was associated with lymph node invasion (χ2 = 4.27, P = 0.039). ROC curves showed that sSYPL1 performed superbly in distinguishing CRC patients from controls (AUC: 0.9481; sensitivity: 86.09%, specificity: 91.01%) and adenoma (AUC: 0.8631; sensitivity: 98.68%, specificity: 78.08%). This performance was much better than that of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9). Even for patients with low CEA levels (under 5 ng/mL), SYPL1 maintained the same high performance for identification of CRC. Furthermore, sSYPL1 levels declined significantly after radical surgery (t = 5.903, P < 0.0001). CONCLUSION: sSYPL1 might be an outstanding marker for CRC diagnosis, especially for patients with low CEA levels.

Intrinsic Luminescence from Nonaromatic Biomolecules.

Novel emitters that do not contain traditional chromophores but only electron-rich moieties (e. g. amine, C=O, -OH, ether, and imide), which are classified as nonconventional luminophores, have been more frequently reported. Although more and more examples have been demonstrated, their emission mechanism remains unclear. The clustering-triggered emission (CTE) mechanism has previously been proposed to rationalize the luminescence of unconventional chromophores. Moreover, great attention has been paid to the distinctive inherent luminescence from nonaromatic biomolecules such as cellulose, starch, sugars, and nonaromatic amino acids and proteins. In this Review, we summarize these unconventional biomolecular luminophores and apply the CTE mechanism to rationalize such a phenomenon. This Review may shed new light on the understanding of intrinsic emission of nonaromatic biomolecules and decipher the intrinsic fluorescence from cells and tissues.

Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey.

BACKGROUND: This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a central Chinese urban population. METHODS: From December 2017 to June 2018, a total of 5231 subjects were randomly enrolled from 3 communities in 3 districts of Zhengzhou. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min.1.73m2 or urinary albumin to creatinine ratio ≥ 30 mg/g (albuminuria). Diabetic subjects with systolic blood pressure > 140 mmHg, albuminuria or an eGFR less than 60 mL/min/1.73 m2 were classified as having DKD. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urine specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and sex-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduced renal function were analyzed by binary and ordinal logistic regression. RESULTS: The overall adjusted prevalence of CKD was 16.8% (15.8-17.8%) and that of DKD was 3.5% (3.0-4.0%). Decreased renal function was detected in 132 participants (2.9, 95% confidence interval [CI]: 2.5-3.2%), whereas albuminuria was found in 858 participants (14.9, 95% CI: 13.9-15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9-8.6%) and that of albuminuria was 45.3% (95% CI = 40.4-50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1-52.9%). The results of the binary and ordinal logistic regression indicated that the factors independently associated with a higher risk of reduced eGFR and albuminuria were older age, sex, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. CONCLUSIONS: Our study shows the current prevalence of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.