C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

A PTER-dependent pathway of taurine metabolism linked to energy balance.

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in biosynthesis of taurine from cysteine as well as the downstream derivatization of taurine into secondary taurine metabolites4,5. One such taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by diverse physiologic perturbations that alter taurine and/or acetate flux, including endurance exercise7, nutritional taurine supplementation8, and alcohol consumption6,9. While taurine N-acetyltransferase activity has been previously detected in mammalian cells6,7, the molecular identity of this enzyme, and the physiologic relevance of N-acetyltaurine, have remained unknown. Here we show that the orphan body mass index-associated enzyme PTER (phosphotriesterase-related)10 is the principal mammalian taurine N-acetyltransferase/hydrolase. In vitro, recombinant PTER catalyzes bidirectional taurine N-acetylation with free acetate as well as the reverse N-acetyltaurine hydrolysis reaction. Genetic ablation of PTER in mice results in complete loss of tissue taurine N-acetyltransferase/hydrolysis activities and systemic elevation of N-acetyltaurine levels. Upon stimuli that increase taurine levels, PTER-KO mice exhibit lower body weight, reduced adiposity, and improved glucose homeostasis. These phenotypes are recapitulated by administration of N-acetyltaurine to wild-type mice. Lastly, the anorexigenic and anti-obesity effects of N-acetyltaurine require functional GFRAL receptors. Together, these data uncover enzymatic control of a previously enigmatic pathway of secondary taurine metabolism linked to energy balance.

Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer.

INTRODUCTION: The aim of this study was to investigate the epigenetic regulation and underlying mechanism of NRIP3 in colorectal cancer (CRC). METHODS: Eight cell lines (SW480, SW620, DKO, LOVO, HT29, HCT116, DLD1, and RKO), 187 resected margin samples from colorectal cancer tissue, 146 cases with colorectal adenomatous polyps, and 308 colorectal cancer samples were used. Methylation-specific PCR, Western blotting, RNA interference assay, and a xenograft mouse model were used. RESULTS: NRIP3 exhibited methylation in 2.7% (5/187) of resected margin samples from colorectal cancer tissue, 32.2% (47/146) of colorectal adenomatous polyps, and 50.6% (156/308) of CRC samples, and the expression of NRIP3 was regulated by promoter region methylation. The methylation of NRIP3 was found to be significantly associated with late onset (at age 50 years or older), poor tumor differentiation, lymph node metastasis, and poor 5-year overall survival in CRC (all P < 0.05). In addition, NRIP3 methylation was an independent poor prognostic marker ( P < 0.05). NRIP3 inhibited cell proliferation, colony formation, invasion, and migration, while induced G1/S arrest. NRIP3 suppressed CRC growth by inhibiting PI3K-AKT signaling both in vitro and in vivo . Methylation of NRIP3 sensitized CRC cells to combined PI3K and ATR/ATM inhibitors. DISCUSSION: NRIP3 was frequently methylated in both colorectal adenomatous polyps and CRC. The methylation of NRIP3 may potentially serve as an early detection, late-onset, and poor prognostic marker in CRC. NRIP3 is a potential tumor suppressor. NRIP3 methylation is a potential synthetic lethal marker for combined PI3K and ATR/ATM inhibitors.

Clinical outcomes and medical resource utilization of toripalimab combination therapy versus bevacizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer.

OBJECTIVE: This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China. METHODS: Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled. RESULTS: Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p < .001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p < .0001) and AE-related costs ($4,500.2 vs. $784.4, p < .0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p < .0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%). CONCLUSION: Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs.

Molecular epidemiological characteristics of carbapenem-resistant Pseudomonas aeruginosa clinical isolates in southeast Shanxi, China.

OBJECTIVES: Infection by carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious clinical problem worldwide. However, the molecular epidemiology of the clinical isolates varies depending on the region. This study was conducted to analyse the resistance phenotype and clarify the genetic and epidemiological properties of CRPA clinical isolates from southeast Shanxi, China. METHODS: Fifty-seven isolates of CRPA were collected from a hospital in this region. These isolates were reidentified by MALDI-TOF and subjected to whole-genome sequencing by next-generation sequencing. Phylogenetic trees were constructed based on single nucleotide polymorphisms (SNPs), after which multilocus sequence typing (MLST) was performed and antimicrobial resistance genes were identified. RESULTS: All the 57 CRPA isolates carried at least one kind of gene encoding carbapenemase, such as blaIMP-1, blaIMP-10, blaOXA-10, blaOXA-395, blaOXA-396, blaOXA-485, blaOXA-486, blaOXA-488, blaOXA-494, and blaOXA-50. The isolates harboured AIM-1, CMY-51, mecD, and NmcR genes and carried one kind of Pseudomonas-derived cephalosporinase (PDC) ß-lactamase-encoding gene, such as blaPCD-1 to blaPCD-3, blaPCD-5, or blaPCD-7 to blaPCD-10. Two isolates were found to harbour the aminoglycoside-modifying enzyme genes aadA1 and aadA7; however, no isolates were found to harbour genes encoding 16S rRNA methylase or quinolone resistance-related genes. These CRPA isolates belonged to various sequence types (STs), two of which, namely, ST235 and ST277, were high-risk types. CONCLUSIONS: Our findings indicate that CRPA isolates carrying resistance genes with unique regional characteristics are spreading in this region, with a high diversity of STs, especially in high-risk clones. These findings highlight the necessity for further measures to prevent CRPA spread in Shanxi.

Identification of Novel Stemness-based Subtypes and Construction of a Prognostic Risk Model for Patients with Lung Squamous Cell Carcinoma.

BACKGROUND: Although cancer stem cells (CSCs) contribute to tumorigenesis, progression, and drug resistance, stemness-based classification and prognostic signatures of lung squamous cell carcinoma (LUSC) remain unclarified. This study attempted to identify stemness-based subtypes and develop a prognostic risk model for LUSC. METHODS: Based on RNA-seq data from The Cancer Genome Atlas (TCGA), Gene-Expression Omnibus (GEO) and Progenitor Cell Biology Consortium (PCBC), mRNA expression-based stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR) algorithm. A weighted gene coexpression network (WGCNA) was employed to identify stemness subtypes. Differences in mutation, clinical characteristics, immune cell infiltration, and antitumor therapy responses were determined. We constructed a prognostic risk model, followed by validations in GEO cohort, pan-cancer and immunotherapy datasets. RESULTS: LUSC patients with subtype C2 had a better prognosis, manifested by higher mRNAsi, higher tumor protein 53 (TP53) and Titin (TTN) mutation frequencies, lower immune scores and decreased immune checkpoints. Patients with subtype C2 were more sensitive to Imatinib, Pyrimethamine, and Paclitaxel therapy, whereas those with subtype C1 were more sensitive to Sunitinib, Saracatinib, and Dasatinib. Moreover, we constructed stemness-based signatures using seven genes (BMI1, CCDC51, CTNS, EIF1AX, FAM43A, THBD, and TRIM68) and found high-risk patients had a poorer prognosis in the TCGA cohort. Similar results were found in the GEO cohort. We verified the good performance of risk scores in prognosis prediction and therapy responses. CONCLUSION: The stemness-based subtypes shed novel insights into the potential roles of LUSC-stemness in tumor heterogeneity, and our prognostic signatures offer a promising tool for prognosis prediction and guide therapeutic decisions in LUSC.

Rice husk hydrochar prepared by hydrochloric acid assisted hydrothermal carbonization for levofloxacin removal in bioretention columns.

Hydrochars are promising adsorbents in pollutant removal for water treatment. Herein, hydrochloric acid (HCl) co-hydrothermally treated hydrochars were prepared from rice husk biomass at 180 °C via a one-step hydrothermal method. Adsorption behaviors of levofloxacin (LVX) on hydrochars were evaluated. The specific surface area and pore volume of the hydrochar synthesized in 5 mol/L HCl (5H-HC) were almost 17 and 8 times of untreated hydrochar, respectively. The 5H-HC sample exhibited the highest LVX adsorption capability at room temperature (107 mg/g). Thermodynamic experimental results revealed that adsorption was a spontaneous endothermic process. Yan model provided the best description of the breakthrough behavior of LVX in bioretention column, indicating that the adsorption on the samples involved several rate-limiting factors including diffusion and mass transfer. The results show that facile HCl co-hydrothermal carbonization of waste biomass can produce novel hydrochars with high LVX adsorption ability.

The effects of community-based home health care on the physical and mental health of older adults with chronic diseases.

PURPOSE: This study aimed to explore the effects of community-based home health care (HHC) on the physical and mental health of older adults with chronic diseases in China. METHODS: The study data were retrieved from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey. Ordinary least squares regression model was used to assess the effects of community-based HHC on the health. Entropy balancing was used to test the robustness of the regression results. RESULTS: A total of 5571 older adults with chronic diseases were included. The results showed that older adults who had received community-based HHC reported significantly better self-rated health (coefficient = 0.051, 95%CI [0.004, 0.098]), less physical discomfort (coefficient = - 0.021, 95%CI [- 0.042, - 0.001]), lower depression scores (coefficient = - 0.263, 95%CI [- 0.490, - 0.037]), and lower anxiety scores (coefficient = - 0.233, 95%CI [- 0.379, - 0.088]) compared with those who had not received community-based HHC. Overall, community-based HHC conferred greater positive effects on the health of rural older adults, older adults with multiple chronic diseases, and older adults with low incomes. CONCLUSION: Community-based HHC was beneficial for improving self-rated health and reducing physical discomfort, depression, and anxiety in older adults with chronic diseases, thus improving their quality of life. It is important to promote its development nationwide in China.

Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advanced EGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study.

Background: In the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations. Methods: We enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups. Results: After PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups. Conclusions: In real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Long-term outcomes of esophageal and gastric cancer patients with cardiovascular and metabolic diseases: A two-center propensity score-matched cohort study.

Background and Objectives: An increased risk of cardiovascular and metabolic diseases (CVMDs) among patients with cancer suggests a potential link between CVMD and cancer. The impact of CVMD on the survival time of patients with esophageal and gastric cancer remains unknown. We aimed to determine the incidence of CVMD and its impact on the longterm outcomes in esophageal and gastric cancer patients. Methods: A total of 2074 cancer patients were enrolled from January 1, 2007 to December 31, 2017 in two hospitals, including 1205 cases of esophageal cancer and 869 cases of gastric cancer, who were followed up for a median of 79.8 and 79.3 months, respectively. Survival time was analyzed using the Kaplan-Meier method before and after propensity score matching. Results: The incidence of CVMD in patients with esophageal and gastric cancer was 34.1% (411/1205) and 34.3% (298/869), respectively. The effects of hypertension, diabetes, and stroke on the long-term survival of esophageal and gastric cancer patients were not significant (all P > 0.05). The survival time was significantly longer in esophageal cancer patients without ischemic heart disease than in patients with ischemic heart disease, both before matching (36.5 vs. 29.1 months, P = 0.027) and after matching (37.4 vs. 27.9 months, P = 0.011). The survival time in gastric cancer patients without ischemic heart disease was significantly longer than in patients with ischemic heart disease, both before (28.4 vs.17.5 months, P = 0.032) and after matching (29.5 vs.17.5 months, P = 0.02). Conclusion: The survival time of esophageal and gastric cancer patients with ischemic heart disease was significantly reduced compared to that of esophageal and gastric cancer patients without ischemic heart disease.

Opportunities and challenges of protein-based targeted protein degradation.

In the 20 years since the first report of a proteolysis targeting chimeric (PROTAC) molecule, targeted protein degradation (TPD) technologies have attempted to revolutionize the fields of chemical biology and biomedicine by providing exciting research opportunities and potential therapeutics. However, they primarily focus on the use of small molecules to recruit the ubiquitin proteasome system to mediate target protein degradation. This then limits protein targets to cytosolic domains with accessible and suitable small molecule binding pockets. In recent years, biologics such as proteins and nucleic acids have instead been used as binders for targeting proteins, thereby expanding the scope of TPD platforms to include secreted proteins, transmembrane proteins, and soluble but highly disordered intracellular proteins. This perspective summarizes the recent TPD platforms that utilize nanobodies, antibodies, and other proteins as binding moieties to deplete challenging targets, either through the ubiquitin proteasome system or the lysosomal degradation pathway. Importantly, the perspective also highlights opportunities and remaining challenges of current protein-based TPD technologies.

Aryldiazonium Salt-Triggered [2 + 2 + 1] Heteroannulation of Indoles by an Arylhydrazone Radical-Relayed 1,5-Hydrogen Atom Transfer.

An unprecedented three-component [2 + 2 + 1] annulation cascade of indoles with aryldiazonium salts and polyhalomethanes or acetone is presented by dual hydrogen atom transfer (HAT) and C-H functionalization. By employing readily accessible aryldiazonium salts as the radical initiators and electrophiles and polyhalomethanes and acetone as the C1 units, this method unprecedentedly constructs a pyrazole ring on an indole ring skeleton through the formation of two C-N bonds and a C-C bond in a single reaction.

Importance of Chain Length in Propagation Reaction on •OH Formation during Ozonation of Wastewater Effluent.

During the ozonation of wastewater, hydroxyl radicals (•OH) induced by the reactions of ozone (O3) with effluent organic matters (EfOMs) play an essential role in degrading ozone-refractory micropollutants. The •OH yield provides the absolute •OH formation during ozonation. However, the conventional "tert-Butanol (t-BuOH) assay" cannot accurately determine the •OH yield since the propagation reactions are inhibited, and there have been few studies on •OH production induced by EfOM fractions during ozonation. Alternatively, a "competitive method", which added trace amounts of the •OH probe compound to compete with the water matrix and took initiation reactions and propagation reactions into account, was used to determine the actual •OH yields (Φ) compared with that obtained by the "t-BuOH assay" (φ). The Φ were significantly higher than φ, indicating that the propagation reactions played important roles in •OH formation. The chain propagation reactions facilitation of EfOMs and fractions can be expressed by the chain length (n). The study found significant differences in Φ for EfOMs and fractions, precisely because they have different n. The actual •OH yield can be calculated by n and φ as Φ = φ (1 + n)/(nφ + 1), which can be used to accurately predict the removal of micropollutants during ozonation of wastewater.

Pd-Catalyzed Intermolecular Carbonylative Dearomatization of Arylamines with Propargylic Acetates for Synthesis of Bridged Polycyclic Lactams.

A new palladium-catalyzed multicomponent dearomatization of arylamines with CO and propargylic acetates for the synthesis of bridged polycyclic lactams is described. This method allows double annulation at the ipso and para positions of the amino group to form four new bonds, three C-C bonds and one C-N bond. DFT calculations and experimental studies indicate that the efficient formation of the allenecarboxanilide intermediate is the key step to achieve the dearomative transformation.

Molecular profiling and prognostic biomarkers in chinese non-small cell lung cancer cohort.

INTRODUCTION: Comprehensive information about the genome analysis and its prognostic values of NSCLC patients in Chinese population are still needed. PATIENTS: A total of 117 Chinese patients with NSCLC were enrolled in this study. Tumor tissues or blood were collected and sequenced by targeted next-generation sequencing of 556 cancer related genes. The associations between clinical outcomes and clinical characteristics, TMB, mutated genes, treatment therapies were analyzed using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model. RESULTS: A total of 899 mutations were identified by targeted NGS. The most frequently mutations included EGFR (47%), TP53 (46%), KRAS (18%), LRP1B (12%) and SPTA1 (10%). Patients with mutant TP53, PREX2, ARID1A, PTPRT and PIK3CG had lower median overall survival (OS) than those patients with wild-type (P = 0.0056, P < 0.001, P < 0.0001, P < 0.0001 and P = 0.036, respectively). Using a multivariate Cox regression model, PREX2 (P < 0.001), ARID1A (P < 0.001) and PIK3CG (P = 0.04) were independent prognostic factors in NSCLC. In the patients received chemotherapy, squamous patients had a significantly longer median OS than adenocarcinoma patients (P = 0.011). In the patients received targeted therapy, adenocarcinoma patients had a significantly longer survival period than squamous patients (P = 0.01). CONCLUSIONS: Our study provided comprehensive genomic alterations in a cohort of Chinese NSCLC. We also identified new prognostic biomarkers, which could provide potential clues for targeted therapies.

Genetic Diversity of Polymyxin-Resistance Mechanisms in Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae: a Multicenter Study in China.

Polymyxin has been the last resort to treat multidrug-resistant Klebsiella pneumonia. However, recent studies have revealed that polymyxin-resistant carbapenem-resistant Klebsiella pneumonia (PR-CRKP) emerged due to the mutations in chromosomal genes or the plasmid-harboring mcr gene, leading to lipopolysaccharide modification or efflux of polymyxin through pumps. Further surveillance was required. In the present study we collected PR-CRKP strains from 8 hospitals in 6 provinces/cities across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features by whole-genome sequencing (WGS). The broth microdilution method (BMD) was performed to determine the MIC of polymyxin. Of 662 nonduplicate CRKP strains, 15.26% (101/662) were defined as PR-CRKP; 10 (9.90%) were confirmed as Klebsiella quasipneumoniae by WGS. The strains were further classified into 21 individual sequence types (STs) by using multilocus sequence typing (MLST), with ST11 being prevalent (68/101, 67.33%). Five carbapenemase types were identified among 92 CR-PRKP, blaKPC-2 (66.67%), blaNDM-1 (16.83%), blaNDM-5 (0.99%), blaIMP-4 (4.95%), and blaIMP-38 (0.99%). Notably, 2 PR-CRKP strains harbored both blaKPC-2 and blaNDM-1. The inactivation of mgrB, associated significantly with high-level polymyxin resistance, was mainly caused by the insertion sequence (IS) insertion (62.96%, 17/27). Furthermore, acrR was inserted coincidently by ISkpn26 (67/101, 66.33%). The deletion or splicing mutations of crrCAB were significantly associated with ST11 and KL47 (capsule locus types), and diverse mutations of the ramR gene were identified. Only one strain carried the mcr gene. In summary, the high IS-inserted mgrB inactivation, the close relationship between ST11 and the deletion or splicing mutations of the crrCAB, and the specific features of PR-K. quasipneumoniae constituted notable features of our PR-CRKP strains in China. IMPORTANCE Polymyxin-resistant CRKP is a serious public health threat whose resistance mechanisms should be under continuous surveillance. Here, we collected 662 nonduplicate CRKP strains across China to identify the carbapenemase and polymyxin resistance genes and epidemiological features. Polymyxin resistance mechanism in 101 PR-CRKP strains in China were also investigated, 9.8% of which (10/101) were K. quasipneumoniae, as determined via WGS, and inactivation of mgrB remained the most crucial polymyxin resistance mechanism, significantly related to high-level resistance. Deletion or splicing mutations of crrCAB were significantly associated with ST11 and KL47. Diverse mutations of the ramR gene were identified. The plasmid complementation experiment and mRNA expression analysis further confirmed that the mgrB promoter and ramR played a critical role in polymyxin resistance. This multicenter study contributed to the understanding of antibiotic resistance forms in China.

Prognostic Value of Geriatric Nutritional Risk Index for Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this review was to collate evidence on the prognostic ability of the geriatric nutritional risk index (GNRI) for predicting overall survival (OS) and disease-free survival (DFS) in non-small cell lung cancer (NSCLC). METHODS: The datasets of PubMed, Scopus, Embase, CENTRAL, and Google Scholar were searched up to 24 May 2022 for English-language studies reporting the association between GNRI and OS or DFS in NSCLC patients. RESULTS: Eleven studies with 2865 patients were included. We noted that low GNRI was a significant predictor of poor OS (HR: 1.96 95% CI 1.66, 2.30 I2 = 0% p < 0.00001) and poor DFS (HR: 1.74 95% CI: 1.36, 2.23 I2 = 34% p < 0.0001) in NSCLC patients. The results did not change on sensitivity analysis. There was no evidence of publication bias. Most results were significant on subgroup analysis based on study location, tumor stage, therapy type, sample size, and GNRI cut-off. CONCLUSION: Data indicate that GNRI has good prognostic ability in patients with NSCLC. Individuals with low GNRI are at an increased risk of poor OS and DFS. GNRI could be incorporated as a simple, easy-to-use tool for the initial stratification of patients thereby allowing focused treatment plans.

A tunable full-color lanthanide noncovalent polymer based on cucurbituril-mediated supramolecular dimerization.

The construction of lanthanide multicolor luminescent materials with tunable photoluminescence properties has been developed as one of the increasingly significant topics and shown inventive applications in miscellaneous fields. However, fabricating such materials based on synergistically assembly-induced emission rather than simple blending of different fluorescent dyes together still remains a challenge. Herein, we report a europium-based noncovalent polymer with tunable full-color emission, which is constructed from the 2,6-pyridinedicarboxylic acid-bearing bromophenylpyridinium salt. This rationally designed bifunctional component can concurrently serve as a guest molecule and a chelating ligand to associate with cucurbit[8]uril and europium ions, thus leading to the formation of a trichromatic (red-green-blue, RGB) photoluminescent polypseudorotaxane-type noncovalent polymer in aqueous solution. Meanwhile, the full-color emission enclosed within the RGB color triangle could be readily produced by simply tuning the molar ratio of cucurbit[8]uril and europium ions. The lanthanide supramolecular polymer featuring tricolor emission, long lifetime, high photoluminescence efficiency and low cytotoxicity could be further applied in multicolor imaging in a cellular environment. These results provide a new and feasible strategy for the construction of full-color single lanthanide self-assembled nanoconstructs.

Genomic Alterations Identification and Resistance Mechanisms Exploration of NSCLC With Central Nervous System Metastases Using Liquid Biopsy of Cerebrospinal Fluid: A Real-World Study.

Background: Genomic profiling of cerebrospinal fluid (CSF) can be used to detect actionable mutations and guide clinical treatment of non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in real-world settings can confirm the potential of CSF genotyping for guiding therapy in clinical practice. Patients and Methods: We included 1,396 samples from 970 NSCLC patients with CNS metastases in real-world settings. All samples underwent targeted next-generation sequencing of 1,021 cancer-relevant genes. In total, 100 CSF samples from 77 patients who had previously received targeted treatment were retrospectively analyzed to explore the mechanisms of TKI-resistance. Results: For NSCLC patients with CNS metastases, CSF samples were slightly more often used for genomic sequencing in treated patients with only distant CNS metastases compared to other patients (10.96% vs. 0.81-9.61%). Alteration rates in CSF samples were significantly higher than those in plasma, especially for copy number variants (CNV). The MSAFs of CSF samples were significantly higher than those of plasma and tumor tissues (all p <0.001). Remarkably, detection rates of all actionable mutations and EGFR in CSF were higher than those in plasma samples of treated patients (all p <0.0001). For concordance between paired CSF and plasma samples that were simultaneously tested, the MSAF of the CSF was significantly higher than that of matched plasma cfDNA (p <0.001). From multiple comparisons, it can be seen that CSF better detects alterations compared to plasma, especially CNV and structural variant (SV) alterations. CSF cfDNA in identifying mutations can confer the reason for the limited efficacy of EGFR-TKIs for 56 patients (78.87%, 56/71). Conclusions: This real-world large cohort study confirmed that CSF had higher sensitivity than plasma in identifying actionable mutations and showed high potential in exploring underlying resistance mechanisms. CSF can be used in genomics profiling to facilitate the broad exploration of potential resistance mechanisms for NSCLC patients with CNS metastases.

High N Storage but Low N Recovery After Long-Term N-Fertilization in a Subtropical Cunninghamia lanceolata Plantation Ecosystem: A 14-Year Case Study.

Forests are among the most important N pools of all terrestrial ecosystems. Elevated atmospheric N deposition in recent decades has led to increased interest in the influences of N application on forest N cycles. However, accurate assessments of N storage in forest ecosystems remain elusive. We used a 14-year experiment of a Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] plantation to explore how long-term N fertilization affected N storage and recovery rates. Our study plots were located in a field that had been continuously fertilized over 14 years (2004-2017) with urea at rates of 0 (N0, control), 60 (N60, low-N), 120 (N120, medium-N), and 240 (N240, high-N) kg N hm-2a-1. Data were collected that included N content and biomass in the understory, litter, and various plant organs (i.e., leaves, branches, stems, roots, and bark), as well as soil N content and density at different depths. Results showed that the total ecosystem N storage in the N-fertilized plots was 1.1-1.4 times higher than that in the control plots. About 12.36% of the total ecosystem N was stored in vegetation (plant organs, litter, and understory) and 87.64% was stored in soil (0-60 cm). Plant organs, litter, and soil had higher N storage than the understory layer. Significantly higher plant N uptake was found in the medium-N (1.2 times) and high-N (1.4 times) treatments relative to the control. The N recovery rate of the understory layer in the N-fertilized treatments was negative and less than that in the control. Application of long-term N fertilizer to this stand led to a low N recovery rate (average 11.39%) and high loss of N (average 91.86%), which indicate low N use efficiency in the Chinese fir plantation ecosystem. Our findings further clarify the distribution of N in an important terrestrial ecosystem and improve our understanding of regional N cycles.