Molecular Type Research Articles

Environmental contamination with Clostridioides (Clostridium) difficile in Vietnam.

To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile. Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant. Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings.

BIO9: The Addition of High Molecular Weight Linear Polymers Improves Microvascular Perfusion in an Animal Model of Veno-arterial Extracorporeal Circulation.

High molecular weight linear polymers have been used in turbulent flow applications such as crude oil transfer to reduce drag. These polymers have branched into bioengineering applications to improve pressure changes within the macrocirculation and improve RBC distribution within the microcirculation. The current study aims to determine whether the addition of these polymers to priming fluids used for veno-arterial extracorporeal circulation (VA-ECC) procedures improve microvascular flow and tissue oxygenation. To assess the microcirculation, male Golden Syrian hamsters were instrumented with a dorsal skinfold window chamber, and an exteriorized carotid artery catheter was implanted for arterial blood and blood pressure access. After baseline (BL) measurements were taken, the hamster underwent surgery under isoflurane to insert a drainage catheter into the jugular vein. A heparin bolus (0.05 IU/g) was then provided, and the animal was connected to the VA-ECC circuit. The circuit, consisting of a peristaltic pump and bubble trap, was primed with lactated ringers (LR, control), LR with 5 ppm of 500 kDa polyethylene glycol (PEG500k) or LR with 5 ppm of 3500kDa polyethylene glycol (PEG3500k). Blood flow was ramped up over 15 minutes, maintained at 15% of the animal’s cardiac output for 60 minutes, then ramped down over 15 minutes. The animal was then surgically closed and placed on a heating pad and allowed at least 30 minutes to wake up from the anesthetic plane before taking measurements at 1, 2, and 24 hours after VA-ECC. Capillary perfusion (Figure 1) within the skinfold preparation showed a significant decrease immediately post-ECC for all three groups. However, the PEG3500k group consistently showed significant increase in functional capillary density (FCD) as compared to both other groups after ECC. 24 hrs after ECC, FCD was recovered close to BL levels for both PEG groups, while the LR control did not. Arteriole and venule velocity (Figure 2) was significantly elevated at both 1 and 2 hrs post-ECC for the PEG3500k group when compared to the other two groups. Arteriole flow for the PEG3500k was significantly improved over the LR control at 24 hrs post-ECC, and was significantly higher than BL levels. Hemoglobin saturation within arterioles and venules (Figure 3) revealed that PEG3500k had higher venule saturation at 1 and 2 hrs post-ECC compared to both other groups. The results indicate that the use of PEG3500k improved microvascular perfusion acutely post-ECC, and continued to up to 24 hrs afterwards. The most important changes were in arteriole perfusion and FCD, since that directly impacts oxygen delivery and metabolic washout respectively. Ultimately, this aids in maintaining organ function and preventing the development of ischemic injury and inflammatory cascades. Future studies could optimize the molecular weight, concentration, and type of polymer, along with testing in a clinical ECC circuit to determine hemodynamic changes.Figure 1. Functional capillary density (FCD), normalized to baseline (BL, represented by the dotted line). † P < 0.05 as compared to BL, within each group. * P < 0.05; ** P < 0.01; *** P < 0.001 between groups, at each timepoint.Figure 2. Perfusion within the microcirculation. From top to bottom: diameter, velocity, blood flow. Arterioles are on the left, while venules are on the right. Note that all values were normalized to baseline (BL, represented by the dashed line) and that blood flow was calculated from the diameter and velocity measurements of each vessel. Bar plots represent mean and standard deviation. † P < 0.05 as compared to BL, within each group. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001 between groups, at each timepoint.Figure 3. Hemoglobin oxygen saturation within the microcirculation. Top = arterioles, bottom = venules. Bar plots show mean and standard deviation. † P < 0.05 as compared to BL, within each group. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001 between groups, at each timepoint.

Synthesis and Characterization of PCL-Idebenone Nanoparticles for Potential Nose-to-Brain Delivery.

The present work is focused on the preparation of an optimal model of poly-ε-caprolactone nanoparticles as potential carriers for nasal administration of idebenone. A solvent/evaporation technique was used for nanoparticle preparation. Poly-ε-caprolactone with different molecular weights (14,000 and 80,000 g/mol) was used. Polysorbate 20 and Poloxamer 407, alone and in combination, were used as emulsifiers at different concentrations to obtain a stable formulation. The nanoparticles were characterized using dynamic light scattering, SEM, TEM, and FTIR. The resulting structures were spherical in shape and their size distribution depended on the type of emulsifier. The average particle size ranged from 188 to 628 nm. The effect of molecular weight and type of emulsifier was established. Optimal models of appropriate size for nasal administration were selected for inclusion of idebenone. Three models of idebenone-loaded nanoparticles were developed and the effect of molecular weight on the encapsulation efficiency was investigated. Increased encapsulation efficiency was found when poly-ε-caprolactone with lower molecular weight was used. The molecular weight also affected the drug release from the nanostructures. Dissolution study data were fitted into various kinetic models and the Korsmeyer-Peppas model was found to be indicative of the release mechanism of idebenone.

Front Cover: Meso‐substituted Metalloporphyrin‐based Composites for Electrocatalytic Oxygen Reduction Reactions (ChemNanoMat 6/2023)

The molecular structure and type of carbon support influence the properties of meso-substituted metalloporphyrin-based composites for electrocatalytic oxygen reduction reactions (ORRs). This review discusses these effects in detail and provides insights into structure-performance relationships to support the advancement of non-platinum electrocatalysts. More information can be found in the Review by Jun Chen, Long Zhao et al.

ACID-BASE PROPERTIES AND VOLATILIITY OF FLUORIDES OF s-, p-, d-METALS

A correlation between acid-base properties and volatility parameters (temperature and enthalpy of vaporization) of fluorides of s-, p-, and d-metals was revealed. As a characteristic of acid-base properties, the basicity parameter proposed in the work, based on the size-charge characteristics of the ions that make up the compound, is taken. The value of the basicity parameter naturally decreases from fluorides of low-valent metals (I–III) to fluorides of highvalent metals (IV–VII). The indicated cation substitution results in a significant increase in the volatility of compounds, which is explained by a change in the type of crystal structure from ionic-covalent to molecular one typical for acid-type fluorides. Metal fluorides with intermediate values of the basicity parameter (Zr(IV), Hf(IV), Al(III)) are characterized by significantly higher values of temperature and evaporation enthalpy, that is, lower volatility compared to metal fluorides with a molecular type of structure, which indicates the manifestation of ionic-covalent type of structure. The entropy of evaporation of metal fluorides with a molecular type of structure, as well as with an ionic-covalent type, is characterized by low values (80 ÷ 140 J/mol∙K), which indicates minor changes in the structure of the molecules during evaporation. On the other hand, in the case of compounds with intermediate basicity (ZrF4, AlF3), the values of the entropy of evaporation are significantly higher (over 180 J/mol∙K), which indicates significant structural changes. A method of experimental evaluation of the volatility of compounds by measuring the rate of the coating condensation on the substrate is proposed. It is shown the possibility of combining metal fluorides into complex compounds based on the principle of basicity and on the known values of the evaporation temperature and the conventional temperature. The nature of the influence of anionic substitution in Zirconium compounds with the same charge of ions (F– → Cl– → Br– → l–) and with a change in charge (F– → O2– → N3– → C4–) on the basicity and volatility of the compounds was established. If in the first case there are no significant changes in the nature of the compounds, then in the second there is a sharp increase in melting and evaporation temperatures due to an increase in basicity.

Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker.

The liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC. The publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein-protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells. We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1. We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.

Phosphatidylinositol kinases in GtoPdb v.2023.1

Phosphatidylinositol may be phosphorylated at either 3- or 4- positions on the inositol ring by PI 3-kinases or PI 4-kinases, respectively.Phosphatidylinositol 3-kinasesPhosphatidylinositol 3-kinases (PI3K, provisional nomenclature) catalyse the introduction of a phosphate into the 3-position of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) or phosphatidylinositol 4,5-bisphosphate (PIP2). There is evidence that PI3K can also phosphorylate serine/threonine residues on proteins. In addition to the classes described below, further serine/threonine protein kinases, including ATM (Q13315) and mTOR (P42345), have been described to phosphorylate phosphatidylinositol and have been termed PI3K-related kinases. Structurally, PI3Ks have common motifs of at least one C2, calcium-binding domain and helical domains, alongside structurally-conserved catalytic domains. wortmannin and LY 294002 are widely-used inhibitors of PI3K activities. wortmannin is irreversible and shows modest selectivity between Class I and Class II PI3K, while LY294002 is reversible and selective for Class I compared to Class II PI3K.Class I PI3Ks (EC 2.7.1.153) phosphorylate phosphatidylinositol 4,5-bisphosphate to generate phosphatidylinositol 3,4,5-trisphosphate and are heterodimeric, matching catalytic and regulatory subunits. Class IA PI3Ks include p110α, p110β and p110δ catalytic subunits, with predominantly p85 and p55 regulatory subunits. The single catalytic subunit that forms Class IB PI3K is p110γ. Class IA PI3Ks are more associated with receptor tyrosine kinase pathways, while the Class IB PI3K is linked more with GPCR signalling.Class II PI3Ks (EC 2.7.1.154) phosphorylate phosphatidylinositol to generate phosphatidylinositol 3-phosphate (and possibly phosphatidylinositol 4-phosphate to generate phosphatidylinositol 3,4-bisphosphate). Three monomeric members exist, PI3K-C2α, β and β, and include Ras-binding, Phox homology and two C2 domains.The only class III PI3K isoform (EC 2.7.1.137) is a heterodimer formed of a catalytic subunit (VPS34) and regulatory subunit (VPS15).Phosphatidylinositol 4-kinasesPhosphatidylinositol 4-kinases (EC 2.7.1.67) generate phosphatidylinositol 4-phosphate and may be divided into higher molecular weight type III and lower molecular weight type II forms.

An integrated signature of extracellular matrix proteins and a diastolic function imaging parameter predicts post-MI long-term outcomes.

Patients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes. In a prospective AMI cohort in New Zealand (N = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides). Using a network-based data integration approach (iOmicsPASS+), we identified predictive signatures of long-term secondary outcomes based on plasma protein, lipid, imaging markers and clinical biomarkers and assessed the prognostic potential in an independent cohort from Singapore (N = 190). The post-discharge levels of plasma proteins and lipids showed strong correlations within each molecular type, reflecting concerted homeostatic regulation after primary MI events. However, the two molecular types were largely independent with distinct correlation structures with established prognostic imaging parameters and clinical biomarkers. To deal with massively correlated predictive features, we used iOmicsPASS + to identify subnetwork signatures of 211 and 189 data features (nodes) predictive of MACE and HF events, respectively (160 overlapping). The predictive features were primarily imaging parameters, including left ventricular and atrial parameters, tissue Doppler parameters, and proteins involved in extracellular matrix (ECM) organization, cell differentiation, chemotaxis, and inflammation. The network signatures contained plasma protein pairs with area-under-the-curve (AUC) values up to 0.74 for HF prediction in the validation cohort, but the pair of NT-proBNP and fibulin-3 (EFEMP1) was the best predictor (AUC = 0.80). This suggests that there were a handful of plasma proteins with mechanistic and functional roles in predisposing patients to the secondary outcomes, although they may be weaker prognostic markers than natriuretic peptides individually. Among those, the diastolic function parameter (E/e' - an indicator of left ventricular filling pressure) and two ECM proteins, EFEMP1 and follistatin-like 3 (FSTL3) showed comparable performance to NT-proBNP and outperformed left ventricular measures as benchmark prognostic factors for post-MI HF. Post-discharge levels of E/e', EFEMP1 and FSTL3 are promising complementary markers of secondary adverse outcomes in AMI patients.

A Statistical Analysis of Galactic Radio Supernova Remnants

We present a revised table of 390 Galactic radio supernova remnants (SNRs) and their basic parameters. Statistical analyses are performed on SNR diameters, ages, spectral indices, Galactic heights, and spherical symmetries. Furthermore, the accuracy of distances estimated using the Σ–D relation is examined. The arithmetic mean of the Galactic SNR diameters is 30.5 pc with standard error 1.7 pc and standard deviation 25.4 pc. The geometric mean and geometric standard deviation factor of Galactic SNR diameters is 21.9 pc and 2.4, respectively. We estimate ages of 97 SNRs and find a supernova (SN) birth rate lower than, but within 2σ of, currently accepted values for the SN birth rate. The mean spectral index of shell-type SNRs is −0.51 ± 0.01 and no correlations are found between spectral indices and the SNR parameters of molecular cloud association, SN type, diameter, Galactic height, and surface brightness. The Galactic height distribution of SNRs is best described by an exponential distribution with a scale height of 48 ± 4 pc. The spherical symmetry measured by the ovality of radio SNRs is not correlated to any other SNR parameters considered here or to explosion type.

Ki67-PROLIFERATIVE INDEX IN BREAST CANCER AND ITS ASSOCIATION WITH MOLECULAR SUBTYPE, HISTOPATHOLOGICAL GRADE &amp; TYPE - IN A TERTIARY CARE HOSPITAL.

Introduction: Carcinoma of breast is the most frequent malignancy in women worldwide and the second most common cause of fatality in patient with cancer. Prognostic factors are essential in breast cancer diagnosis as they allow high risk patient identication, for whom prognosis can be further improved by an adjuvant therapy. Ki67 proliferative index is a potential marker for predicting the responsiveness to chemotherapy. This present study has been designed to analyze the relationship of Ki67 proliferative index with clinico-pathological factors in eighty diagnosed cases of primary breast carcinoma, according to the molecular subtypes. To compare the e Objective: xpression of Ki67 proliferative index with the molecular subtype, histopathological grade and type of breast carcinoma. The study w Material and Methods: as carried out from October 2019 - September 2021 in the Department of Pathology, M.K.C.G Medical College &amp; Hospital, Odisha. 80 cases received for routine histopathological examination were evaluated for histopathological typing and IHC status – ER, PR, Her2neu &amp; Ki67. 46 cases belonged to T2 followed by Result: T3 and T1. 45% cases were Grade III followed by Grade II and Grade I tumors. 74 cases were IDC NOS, 2 cases Lobular, 2 cases Metaplastic, 1 case Medullary and 1 case Mucinous. High Ki67 index seen in 70.37% cases in T3 category followed by T2 (45.65%) and T1(42.86%). Low Ki67 index is associated with Luminal A followed by Luminal B. High Ki67 index is seen in 83.33% of Grade III tumor but none in Grade I tumor. Whereas, high Ki67 index is found in both Her2neu enriched and Triple Negative breast carcinoma. High Ki67 proliferative index Conclusion: was associated with high grade tumor, Her2/neu enriched and Triple negative tumor. However, there was no signicant relation found in association of ER, PR, Her2/neu and Ki67 with the tumor size

Changes in the structure of polysaccharides under different extraction methods

Changes in the structure of polysaccharides under different extraction methods

Low regularity solutions for the Vlasov–Poisson–Landau/Boltzmann system

In the paper, we are concerned with the nonlinear Cauchy problem on the Vlasov–Poisson–Landau/Boltzmann system around global Maxwellians in a torus or a finite channel. The main goal is to establish the global existence and large time behaviour of small amplitude solutions for a class of low regularity initial data. The molecular interaction type is restricted to the case of hard potentials for two classical collision operators because of the effect of the self-consistent forces. The result extends the one by Duan–Liu–Sakamoto-Strain (Duan et al 2021 Commun. Pure Appl. Math. 74 932–1020) for the pure Landau/Boltzmann equation to the case of the VPL and VPB systems.

Abstract P6-05-13: The Psychological Impacts of COVID-19 on Breast Cancer Patients in China

Abstract Background: Approximately 30% to 50% of breast cancer patients experienced mental distress prior to the advent of COVID.The delayed access to cancer treatment due to the outbreak of COVID -19 pandemic posed a unique challenge to breast cancer patients and caused a significant level of mental distress among them. In the current research, we examined the psychological impacts of COVID on breast cancer patients in China using Symptom Checklist-90-R (SCL-90-R). Method: Participants were breast cancer patients at the outpatient clinic of Xijing hospital. The study was conducted virtually, and the questionnaires were distributed via Wenjuanxing, the Chinese alternative of Qualtrics. The researchers were healthcare workers affiliated with Xijing hospital, and the survey was sent to a breast cancer patient support group which included 1399 cancer patients and 6 healthcare workers. The initial sample consisted of 199 participants who signed an informed consent form to participate in the study. The inclusion criteria were as follows: 1) diagnosed with breast cancer, 2) aged 18 years or above, and 3) had no history of cognitive impairment or previous diagnosis of psychiatric disorders. The validated Mandarin version of the SCL-90-R (Wang, 1984) was then given to the participants to evaluate their psychological status.Categorical variables were summarized as numbers and percentages; continuous variables were described as mean (M) ± standard deviation (SD). Data were analyzed using IBM SPSS Statistics Version 26. Results: Participants (N = 195) filled out the SCL-90 questionnaire in February, 2020. All participants were female breast cancer patients treated at Xijing hospital, among which 16.41%, 36.41%, 19.49%, and 28.21% had respectively received treatment for less than a year, 1-3 years, 3-5 years, and 5 years or more. 64.62% of the patients were at stage I; 0.77% were at stage II and III; 4.62% were at stage IV according to TNM classification. The molecular type of participants is as follows: 47.2% of ER+ HER2-, 31.8% of HER2+, and 21.0% of Triple negative.Participants whose treatments continued to be delayed, on average, reported an elevated general psychopathology score (M = 1.48, SD = 0.47) compared to participants whose treatments were resumed (M = 1.30, SD = 0.34), and the difference was statistically significant, t(193) = 2.96, p = .003, d = 0.44, 95%Cl [0.06, 0.30]. The one-way ANOVA revealed a marginally significant effect of length of treatment delay on general psychopathology score, F(4, 190) = 2.09, p = .08, η^2 = .04. Follow-up multiple comparison analysis showed that participants who had their treatment delayed for 3 weeks to 1 month (M = 1.70, SD = 0.70) reported significantly higher general psychopathology scores than participants whose delay in treatment was less than 1 week (M = 1.34, SD = 0.40), p = .05. General health status (p &amp;lt; .001) and current treatment status (p = .02) are the only two variables that were statistically associated with general psychopathology score.Poorer perceived health status and current delay in treatment were associated with higher general psychopathology score, Additionally, younger age was associated with higher interpersonal sensitivity (p = .01) and hostility (p = .006). Conclusions: We found that breast cancer patients at an advanced stage were more likely to experience psychological symptoms with longer treatment delay, and whose treatments continued to be delayed reported elevated psychological symptoms than individuals whose treatment were resumed, regardless of treatment type. Additionally, a treatment delay of more than three weeks might have exacerbated breast cancer patients’ psychological symptoms, whereas a short-term delay of less than three weeks was less likely to have a significant effect on one’s mental well-being. Table 1. Demographic Characteristics and Health Status of The Participants. Table 2A: Multiple Regression analysis for SCL-90 dimensions. Table 2B: Multiple Regression analysis for SCL-90 dimensions. Citation Format: Yijia Wang, Yuqing Yang, Changjiao Yan, Jixin Yang, Hongliang Wei, Wen Ma, Nanlin Li. The Psychological Impacts of COVID-19 on Breast Cancer Patients in China [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-13.

Antimicrobial Resistance, SCCmec, Virulence and Genotypes of MRSA in Southern China for 7 Years: Filling the Gap of Molecular Epidemiology.

As the prevalence of Staphylococcus aureus infections is of worldwide concern, phenotype and genotype in prevalent MRSA strains require longitudinal investigation. In this study, the antibiotic resistance, virulence gene acquisition, and molecular type were determined on a large scale of nosocomial S. aureus strains in Southern China during 2009-2015. Bacterial identification and antimicrobial susceptibility to 10 antibiotics were tested by Vitek-2. Virulence genes encoding staphylococcal enterotoxins (SEA, SEB, SEC, SED, and SEE), exfoliative toxins (ETA and ETB), Panton-Valentine leukocidin (PVL), and toxic shock syndrome toxin (TSST) were detected by PCR, with SCCmec typing also conducted by multiplex PCR strategy. Genotypes were discriminated by MLST and spaA typing. MLST was performed by amplification of the internal region of seven housekeeping genes. PCR amplification targeting the spa gene was performed for spa typing. No resistance to vancomycin, linezolid, or quinupristin and increase in the resistance to trimethoprim/sulfamethoxazole (55.5%) were identified. A total of nine SCCmec types and subtypes, thirteen STs clustered into thirteen spa types were identified, with ST239-SCCmec III-t037 presenting the predominant methicillin-resistant S. aureus (MRSA) clone. Typically, SCCmec type IX and ST546 were emergent types in China. Isolates positive for both pvl and tsst genes and for both eta and etb genes were also identified. Important findings in this study include: firstly, we have provided comprehensive knowledge on the molecular epidemiology of MRSA in Southern China which fills the gap since 2006 or 2010 from previous studies. Secondly, we have presented the correlation between virulence factors (four major groups) and genotypes (SCCmec, ST and spa types). Thirdly, we have shown evidence for earliest emergence of type I SCCmec from 2012, type VI from 2009 and type XI from 2012 in MRSA from Southern China.

A genomically stable molecular type of gastric cancer as a predictor of peritoneal relapse after radical surgical treatment

A genomically stable molecular type of gastric cancer as a predictor of peritoneal relapse after radical surgical treatment

Molecular taxonomy of nociceptors and pruriceptors.

Molecular taxonomy of nociceptors and pruriceptors.

Metabolic Modeling Identifies a Novel Molecular Type of Glioblastoma Associated with Good Prognosis.

Glioblastoma (GBM) is one of the most aggressive forms of cancer. Although IDH1 mutation indicates a good prognosis and a potential target for treatment, most GBMs are IDH1 wild-type. Identifying additional molecular markers would help to generate personalized therapies and improve patient outcomes. Here, we used our recently developed metabolic modeling method (genome-wide precision metabolic modeling, GPMM) to investigate the metabolic profiles of GBM, aiming to identify additional novel molecular markers for this disease. We systematically analyzed the metabolic reaction profiles of 149 GBM samples lacking IDH1 mutation. Forty-eight reactions showing significant association with prognosis were identified. Further analysis indicated that the purine recycling, nucleotide interconversion, and folate metabolism pathways were the most robust modules related to prognosis. Considering the three pathways, we then identified the most significant GBM type for a better prognosis, namely N+P-. This type presented high nucleotide interconversion (N+) and low purine recycling (P-). N+P--type exhibited a significantly better outcome (log-rank p = 4.7 × 10-7) than that of N-P+. GBM patients with the N+P--type had a median survival time of 19.6 months and lived 65% longer than other GBM patients. Our results highlighted a novel molecular type of GBM, which showed relatively high frequency (26%) in GBM patients lacking the IDH1 mutation, and therefore exhibits potential in GBM prognostic assessment and personalized therapy.

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer.

The burden of incidence rate and mortality of cancer is increasing rapidly, and the development of precise intervention measures for cancer detection and treatment will help reduce the burden and pain of cancer. At present, the sensitivity and specificity of tumor markers such as CEA and CA-125 used clinically are low, while PET, SPECT, and other imaging diagnoses with high sensitivity possess shortcomings, including long durations to obtain formal reports and the inability to identify the molecular pathological type of cancer. Cancer surgery is limited by stage and easy to recur. Radiotherapy and chemotherapy often cause damage to normal tissues, leading to evident side effects. Aptamers can selectively and exclusively bind to biomarkers and have, therefore, gained attention as ligands to be targeted for cancer detection and treatment. Gold nanoparticles (AuNPs) are considered as promising nano carriers for cancer diagnosis and treatment due to their strong light scattering characteristics, effective biocompatibility, and easy surface modification with targeted agents. The aptamer-gold nanoparticles targeting delivery system developed herein can combine the advantages of aptamers and gold nanoparticles, and shows excellent targeting, high specificity, low immunogenicity, minor side effects, etc., which builds a bridge for cancer markers to be used in early and efficient diagnosis and precise treatment. In this review, we summarize the latest progress in the application of aptamer-modified gold nanoparticles in cancer targeted diagnosis and delivery of therapeutic agents to cancer cells and emphasize the prospects and challenges of transforming these studies into clinical applications.

Associated Factors of Spontaneous Hemorrhage in Brain Metastases in Patients with Lung Adenocarcinoma.

Hemorrhage in brain metastases (BMs) from lung cancer is common and associated with a poor prognosis. Research on associated factors of spontaneous hemorrhage in patients with BMs is limited. This study aimed to investigate the predictive risk factors for BM hemorrhage and assess whether hemorrhage affects patient survival. We retrospectively evaluated 159 BMs from 80 patients with lung adenocarcinoma from January 2017 to May 2022. Patients were classified into hemorrhagic and non-hemorrhagic groups. Patient demographics, lung cancer molecular subtype, treatment type, and tumor-node-metastasis stage were compared between the groups. Multivariate generalized estimating equation (GEE) analysis and gradient boosting were performed. To determine whether BM hemorrhage can stratify overall survival after BM (OSBM), univariate survival analysis was performed. In the univariate analysis, hemorrhagic BMs were significantly larger and had a history of receiving combination therapy with tyrosine kinase inhibitor (TKI) and intracranial radiation (p < 0.05). Multivariate GEE showed that tumor size and combination therapy were independent risk factors for BM hemorrhage (p < 0.05). Gradient boosting demonstrated that the strongest predictor of BM hemorrhage was tumor size (variable importance: 49.83), followed by age (16.65) and TKI combined with intracranial radiation (13.81). There was no significant difference in OSBM between the two groups (p = 0.33). Hemorrhage in BMs from lung adenocarcinomas may be associated with BM tumor size and a combination of TKI and intracranial radiotherapy. BM hemorrhage did not affect OSBM.

A Landscape of the Genomic Structure of Cryptococcus neoformans in Colombian Isolates

Cryptococcus neoformans species complexes are recognized as environmental fungi responsible for lethal meningoencephalitis in immunocompromised individuals. Despite the vast knowledge about the epidemiology and genetic diversity of this fungus in different regions of the world, more studies are necessary to comprehend the genomic profiles across South America, including Colombia, considered to be the second country with the highest number of Cryptococcosis. Here, we sequenced and analyzed the genomic architecture of 29 Colombian C. neoformans isolates and evaluated the phylogenetic relationship of these strains with publicly available C. neoformans genomes. The phylogenomic analysis showed that 97% of the isolates belonged to the VNI molecular type and the presence of sub-lineages and sub-clades. We evidenced a karyotype without changes, a low number of genes with copy number variations, and a moderate number of single-nucleotide polymorphisms (SNPs). Additionally, a difference in the number of SNPs between the sub-lineages/sub-clades was observed; some were involved in crucial fungi biological processes. Our study demonstrated the intraspecific divergence of C. neoformans in Colombia. These findings provide evidence that Colombian C. neoformans isolates do not probably require significant structural changes as adaptation mechanisms to the host. To the best of our knowledge, this is the first study to report the whole genome sequence of Colombian C. neoformans isolates.