Chang'E-4 initial spectroscopic identification of lunar far-side mantle-derived materials.

Over 60 years of spacecraft exploration has revealed that the Earth's Moon is characterized by a lunar crust1 dominated by the mineral plagioclase, overlying a more mafic (richer in iron and magnesium) mantle of uncertain composition. Both crust and mantle formed during the earliest stages of lunar evolution when late-stage accretional energy caused a molten rock (magma) ocean, flotation of the light plagioclase, sinking of the denser iron-rich minerals, such as olivine and pyroxene, and eventually solidification2. Very large impact craters can potentially penetrate through the crust and sample the lunar mantle. The largest of these craters is the approximately 2,500-kilometre-diameter South Pole-Aitken (SPA) basin3 on the lunar far side. Evidence obtained from orbiting spacecraft shows that the floor of the SPA basin is rich in mafic minerals4, but their mantle origin is controversial and their in situ geologic settings are poorly known. China's Chang'E-4 lunar far-side lander recently touched down in the Von Kármán crater5,6 to explore the floor of the huge SPA basin and deployed its rover, Yutu-2. Here we report on the initial spectral observations of the Visible and Near Infrared Spectrometer (VNIS)7 onboard Yutu-2, which we interpret to represent the presence of low-calcium (ortho)pyroxene and olivine, materials that may originate from the lunar mantle. Geological context6 suggests that these materials were excavated from below the SPA floor by the nearby 72-km-diameter Finsen impact crater event, and transported to the landing site. Continued exploration by Yutu-2 will target these materials on the floor of the Von Kármán crater to understand their geologic context, origin and abundance, and to assess the possibility of sample-return scenarios.

Rapid quantitative magnetization transfer imaging: Utilizing the hybrid state and the generalized Bloch model.

PURPOSE: To explore efficient encoding schemes for quantitative magnetization transfer (qMT) imaging with few constraints on model parameters. THEORY AND METHODS: We combine two recently proposed models in a Bloch-McConnell equation: the dynamics of the free spin pool are confined to the hybrid state, and the dynamics of the semi-solid spin pool are described by the generalized Bloch model. We numerically optimize the flip angles and durations of a train of radio frequency pulses to enhance the encoding of three qMT parameters while accounting for all eight parameters of the two-pool model. We sparsely sample each time frame along this spin dynamics with a three-dimensional radial koosh-ball trajectory, reconstruct the data with subspace modeling, and fit the qMT model with a neural network for computational efficiency. RESULTS: We extracted qMT parameter maps of the whole brain with an effective resolution of 1.24 mm from a 12.6-min scan. In lesions of multiple sclerosis subjects, we observe a decreased size of the semi-solid spin pool and longer relaxation times, consistent with previous reports. CONCLUSION: The encoding power of the hybrid state, combined with regularized image reconstruction, and the accuracy of the generalized Bloch model provide an excellent basis for efficient quantitative magnetization transfer imaging with few constraints on model parameters.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

Awareness and associated factors of venous thromboembolism in breast cancer surgical patients: a cross-sectional study.

BACKGROUND: Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level. METHODS: A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data. RESULTS: Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital's regional location as significant factors associated with VTE awareness level (p < 0.05). CONCLUSION: This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.

Molecular analysis of 12 Chinese patients with 11ß-hydroxylase deficiency and in vitro functional study of 20 CYP11B1 missense variants.

Steroid 11ß-hydroxylase deficiency (11ß-OHD) is a rare autosomal recessive disorder caused by pathogenic variants of CYP11B1 gene. This study aimed to perform molecular analysis of a Chinese 11ß-OHD series and in vitro functional study of twenty CYP11B1 missense variants. Twelve Chinese patients with clinical diagnosis of 11ß-OHD were included in the study to analyze their molecular etiology. Genomic DNA of patients was extracted to be sequenced all coding exons and intronic flanking sequences of CYP11B1. Fourteen missense variants found in 12 patients mentioned above along with 6 missense variants previously reported by our team were evaluated functionally. Amino acid substitutions were analyzed with computational program to determine their effects on the three-dimensional structure of CYP11B1 protein. Clinical characteristics and hormone levels at baseline of the 18 patients carrying 18 missense variants aforementioned were recorded to perform genotype-phenotype correlation. A total of 21 rare variants including 9 novel and 12 recurrent ones were identified in 12 patients, out of which 17 were missense, 2 were nonsense, 1 was a splice site variant, and 1 was a deletion-insertion variant. Results of in vitro functional study revealed that 3 out of 20 missense mutants (p.Leu3Pro, p.Gly267Ser, and p.Ala367Ser) had partial enzyme activity and the other 17 had little enzymatic activity. The impairment degree of enzymatic activity in vitro functional study was also reflected in the severity degree of interaction change between the wild-type/mutant-type amino acid and its adjacent amino acids in three-dimensional model. In conclusion, the addition of 9 novel variants expands the spectrum of CYP11B1 pathogenic variants. Our results demonstrate that twenty CYP11B1 variants lead to impaired 11ß-hydroxylase activity in vitro. Visualizing these variants in the three-dimensional model structure of CYP11B1 protein can provide a plausible explanation for the results measured in vitro.

High expression of NOTCH2 in gastric adenocarcinoma: A novel early diagnostic target.

BACKGROUND AND AIM: NOTCH2 is overexpressed in gastric cancer (GC), and its enhanced activity is significantly correlated with worse tumor characteristics. We aim to analyze the clinicopathologic correlation between NOTCH2 and the molecular typing of GC by immunohistochemistry and by transcriptional sequencing. METHODS: In this immunohistochemical study, we detected NOTCH2, EBER, P53, HER2, MLH1, MSH2, PMS2, and MSH6 and evaluated the association of NOTCH2 with clinical and histopathological features in a large single-institutional series of gastric adenocarcinomas (n = 488). The correlation was also investigated between immunohistochemical results and survival outcomes. RESULTS: High NOTCH2 expression (2+/3+) was found in 139/488 (27.5%) samples analyzed. NOTCH2 expression was correlated with early stage T1 (P < 0.0001), GC in the fundus (P = 0.0364), and positive P53 status (P = 0.0019). We did not find an association between NOTCH2 and HER2, microsatellite instability, EBER, and overall survival. Through RNA sequencing, it was revealed that NOTCH2 plays an important biological function in the pathogenesis and development of GC. CONCLUSIONS: Our findings suggested that NOTCH2 may be a potential diagnostic target for GC due to the fact that its high expression is closely associated with the early stages of cancer.

Ciceribacter sichuanensis sp. nov., a plant growth promoting rhizobacterium isolated from root nodules of soybean in Sichuan, China.

The fast-growing rhizobia-like strains S101T and S153, isolated from root nodules of soybean (Glycine max) in Sichuan, People's Republic of China, underwent characterization using a polyphasic taxonomy approach. The strains exhibited growth at 20-40 °C (optimum, 28 °C), pH 4.0-10.0 (optimum, pH 7.0) and up to 2.0% (w/v) NaCl (optimum, 0.01%) on Yeast Mannitol Agar plates. The 16S rRNA gene of strain S101T showed 98.4% sequence similarity to the closest type strain, Ciceribacter daejeonense L61T. Major cellular fatty acids in strain S101T included summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C19:0 cyclo ω8c. The predominant quinone was ubiquinone-10. The polar lipids of strain S101T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethyl ethanolamine, phosphatidyl ethanolamine, amino phospholipid, unidentified phosphoglycolipid and unidentified amino-containing lipids. The DNA G + C contents of S101T and S153 were 61.1 and 61.3 mol%, respectively. Digital DNA-DNA hybridization relatedness and average nucleotide identity values between S101T and C. daejeonense L61T were 46.2% and 91.4-92.2%, respectively. In addition, strain S101T promoted the growth of soybean and carried nitrogen fixation genes in its genome, hinting at potential applications in sustainable agriculture. We propose that strains S101T and S153 represent a novel species, named Ciceribacter sichuanensis sp. nov., with strain S101T as the type strain (= CGMCC 1.61309 T = JCM 35649 T).

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

Genomic gain/methylation modification/hsa-miR-132-3p increases RRS1 overexpression in liver hepatocellular carcinoma.

This study aimed to determine the upstream regulatory factors affecting ribosome biogenesis regulator 1 homolog (RRS1) expression and the development and prognosis of liver hepatocellular carcinoma (LIHC). The expression profiles of RRS1 were evaluated in pan-cancer tissues and liver tumor cell lines. The associations of RRS1 with pan-cancer survival, immune infiltrations, immune checkpoints, and drug sensitivity were identified. We explored the potential upstream regulatory mechanisms of RRS1 expression. Hsa-miR-132-3p knockdown, CCK-8 assays, transwell, and wound healing assays were performed to validate the regulatory effect of hsa-miR-132-3p on RRS1 expression and the development of LIHC. Our findings demonstrated that RRS1 was significantly elevated in 27 types of cancers. RRS1 predicts a poor outcome of LIHC, lung adenocarcinoma, head and neck cancer, and kidney papillary cell carcinoma. RRS1 expression showed a significant association with immune cell infiltrates and the expression of immune checkpoints-related genes in LIHC tissues. Increased RRS1 expression may have a negative effect on these anticancer drugs of LIHC. Low methylation of the RRS1 promoter and its genomic gain may elevate RRS1 expression and predict poor prognosis for LIHC. Increased hsa-miR-132-3p expression may elevate RRS1 expression and result in poor prognosis for LIHC. Hsa-miR-132-3p inhibition can decrease RRS1 expression and the development of liver tumor cell lines. Low methylation of the RRS1 promoter, RRS1 genomic gain, and hsa-miR-132-3p upregulation in LIHC may promote RRS1 upregulation and thus lead to the development and poor prognosis for LIHC. RRS1 is a promising therapeutic target for LIHC.

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 µg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

A modified immune cell infiltration score achieves ideal stratification for CD8+ T cell efficacy and immunotherapy benefit in hepatocellular carcinoma.

Immunotherapy, which aims to enhance the function of T cells, has emerged as a novel therapeutic approach for hepatocellular carcinoma (HCC). Nevertheless, the clinical utility of using flow cytometry to assess immune cell infiltration (ICI) is hindered by its cumbersome procedures, prompting the need for more accessible methods. Here, we acquired gene expression profiles and survival data of HCC from TCGA and GSE10186 datasets. The patients were categorized into two clusters of ICI, and a set of 11 characteristic genes responsible for the differentiation performance of these ICI clusters were identified. Subsequently, we successfully developed a modified ICI score (mICIS) by utilizing the expression levels of these genes. The efficacy of our mICIS was confirmed via mass cytometry, flow cytometry, and immunohistochemistry. Our research indicated that the favorable overall survival (OS) rate could be attributed to the improved function of anti-tumor leukocytes rather than their infiltration. Furthermore, we observed that the low score group exhibited lower expression levels of T-cell exhaustion-associated genes, which was confirmed in both HCC tissues from patients and mice, which demonstrated that the benefits of the low scores were due to enhanced active/cytotoxic CD8+ T cells and reduced exhausted CD8+ T cells. Additionally, our mICIS stratified the benefits derived from immunotherapies. Lastly, we observed a misalignment between CD8+ T-cell infiltration and function in HCC. In summary, our mICIS demonstrated proficiency in assessing the OS rate of HCC and offering significant stratified data pertaining to distinct responses to immunotherapy.

Past climate cooling and orogenesis of the Hengduan Mountains have influenced the evolution of Impatiens sect. Impatiens (Balsaminaceae) in the Northern Hemisphere.

BACKGROUND: Impatiens sect. Impatiens is distributed across the Northern Hemisphere and has diversified considerably, particularly within the Hengduan Mountains (HDM) in southwest China. Yet, the infra-sectional phylogenetic relationships are not well resolved, largely due to limited taxon sampling and an insufficient number of molecular markers. The evolutionary history of its diversification is also poorly understood. In this study, plastome data and the most complete sampling to date were used to reconstruct a robust phylogenetic framework for this section. The phylogeny was then used to investigate its biogeographical history and diversification patterns, specifically with the aim of understanding the role played by the HDM and past climatic changes in its diversification. RESULTS: A stable phylogeny was reconstructed that strongly supported both the monophyly of the section and its division into seven major clades (Clades I-VII). Molecular dating and ancestral area reconstruction suggest that sect. Impatiens originated in the HDM and Southeast China around 11.76 Ma, after which different lineages dispersed to Northwest China, temperate Eurasia, and North America, mainly during the Pliocene and Pleistocene. An intercontinental dispersal event from East Asia to western North America may have occurred via the Bering Land Bridge or Aleutian Islands. The diversification rate was high during its early history, especially with the HDM, but gradually decreased over time both within and outside the HDM. Multiple linear regression analysis showed that the distribution pattern of species richness was strongly associated with elevation range, elevation, and mean annual temperature. Finally, ancestral niche analysis indicated that sect. Impatiens originated in a relatively cool, middle-elevation area. CONCLUSIONS: We inferred the evolutionary history of sect. Impatiens based on a solid phylogenetic framework. The HDM was the primary source or pump of its diversity in the Northern Hemisphere. Orogeny and climate change may have also shaped its diversification rates, as a steady decrease in the diversification rate coincided with the uplift of the HDM and climate cooling. These findings provide insights into the distribution pattern of sect. Impatiens and other plants in the Northern Hemisphere.

Complete mitochondrial genome of Thuja sutchuenensis and its implications on evolutionary analysis of complex mitogenome architecture in Cupressaceae.

BACKGROUND: The complex physical structure and abundant repeat sequences make it difficult to assemble the mitogenomes of seed plants, especially gymnosperms. Only approximately 33 mitogenomes of gymnosperms have been reported. However, as the most widely distributed and the second largest family among gymnosperms, Cupressaceae has only six assembled mitogenomes, including five draft mitogenomes and one complete mitogenome, which has greatly hindered the understanding of mitogenome evolution within this large family, even gymnosperms. RESULTS: In this study, we assembled and validated the complete mitogenome of Thuja sutchuenensis, with a size of 2.4 Mb. Multiple sequence units constituted its complex structure, which can be reduced to three linear contigs and one small circular contig. The analysis of repeat sequences indicated that the numbers of simple sequence repeats increased during the evolutionary history of gymnosperms, and the mitogenome of Thuja sutchuenensis harboured abundant extra-long repeats (more than 5 kb). Additionally, the longest repeat sequence identified in these seven gymnosperms also came from the mitogenome of Thuja sutchuenensis, with a length of up to 47 kb. The analysis of colinear blocks and gene clusters both revealed that the orders of mitochondrial genes within gymnosperms was not conserved. The comparative analysis showed that only four tRNAs were shared by seven gymnosperms, namely, trnD-GUC, trnE-UUC, trnI-CAU and trnY-GUA. Furthermore, four genes have undergone potential positive selection in most gymnosperm species, namely, atp8, ccmB, mttB and sdh4. CONCLUSION: We successfully assembled the second complete mitogenome within Cupressaceae and verified that it consisted of multiple sequence units. Our study also indicated that abundant long repeats may contribute to the generation of the complex conformation of the mitogenome of Thuja sutchuenensis. The investigation of Thuja sutchuenensis's mitogenome in our study provides new insight into further understanding the complex mitogenome architecture within gymnosperms.

Phylogenomics and historical biogeography of Hydrangeeae (Hydrangeaceae) elucidate the effects of geologic and climatic dynamics on diversification.

Demonstrating the process of transregional biogeography and mechanisms underlying evolutionary radiations is crucial to understanding biological evolution. Here, we use Hydrangeeae (Hydrangeaceae), a tribe with a unique disjunct distribution and complex trait variations, using a solid phylogenetic framework, to investigate how geographical and climatic factors interact with functional traits to trigger plant evolutionary radiations. We constructed the first highly supported and dated phylogenetic framework using 79 protein-coding genes obtained from 81 plastomes, representing 63 species and all major clades, and found that most extant species originated from asynchronous diversification of two lineages undergoing repeated expansion and retraction, at middle and high latitudes of the Northern Hemisphere between East Asia and North America, during the Eocene to Pleistocene (driven by geologic and climatic dynamics). In accordance with these drivers, interactions of flora between central-eastern China and Japan occurred frequently after the Late Tertiary. We found that resource limitation and range fragmentation probably accelerated the diversification of Hydrangeeae, which supports the resource-use hypothesis. Our study sheds light on the evolutionary radiation and assembly of flora within East Asia, and the East Asian-North American disjunction, through integration of phylogenomic and biogeographic data with functional trait and ecological data.

Clinical characteristics of peripherally inserted central catheter-related complications in cancer patients undergoing chemotherapy: a prospective and observational study.

PURPOSE: The incidence of peripherally inserted central catheter (PICC)-related complications is higher in cancer patients than in noncancer patients. However, the pattern of specific complication occurrence over time remains unclear. The purpose of this study was to investigate the clinical characteristics of PICC-related complications in cancer patients undergoing chemotherapy. METHODS: This prospective, observational study was conducted at a university-affiliated hospital in Western China. Cancer patients undergoing PICC insertion for anticancer treatment were recruited and followed up until the first week after catheter removal. Any complications, including occurrence time and outcomes, were recorded. The trajectory of specific PICC-related complications over time were identify based on the Kaplan‒Meier curve analysis. RESULTS: Of the 233 patients analyzed, nearly half (n = 112/233, 48.1%) developed 150 PICC-related complication events. The most common were symptomatic catheter-related thrombosis (CRT) (n = 37/233, 15.9%), medical adhesive-related skin injury (MARSI) (n = 27/233, 11.6%), and catheter dislodgement (n = 17/233, 7.3%), accounting for 54.0% (n = 81/150, 54.0%) of total complications events. According to Kaplan‒Meier curve analysis, symptomatic CRT, pain, phlebitis, and insertion site bleeding were classified as the "early onset" group mainly occurring within the first month post-insertion. Catheter fracture and catheter-related bloodstream infection were classified as the "late onset" group occurring after the second month post-insertion. MARSI, catheter dislodgement, occlusion, and insertion site infection were classified as the "persistent onset" group persistently occurring during the whole catheter-dwelling period. Among the 112 patients with PICC-related complications, 50 (44.6%) patients had their catheters removed due to complications, and 62 (55.4%) patients successfully retained their catheters until treatment completion through conventional interventions. The major reasons for unplanned catheter removal were catheter dislodgement (n = 12/233, 5.2%), symptomatic CRT (n = 10/233, 4.3%), and MARSI (n = 7/233, 3.0%), accounting for 58.0% (n = 29/50, 58.0%) of the total unplanned catheter removal cases. Catheter dwelling times between patients with complications under successful interventions (130.5 ± 32.1 days) and patients with no complications (138.2 ± 46.4 days) were not significantly different (t = 1.306, p = 0.194; log-rank test = 2.610, p = 0.106). CONCLUSIONS: PICC-related complications were pretty common in cancer patients undergoing chemotherapy. The time distribution of PICC-related complications varied, and medical staff should develop time-specific protocols for prevention. Because more than half of the patients with PICC-related complications could be managed with conventional interventions, PICCs remain a priority for cancer patients undergoing short-term chemotherapy. The study was registered in 02/08/2019 at Chinese Clinical Trial Registry (registration number: ChiCTR1900024890).

Age and Gender-Dependence of Single-and Bi-Exponential T1ρ MR Parameters in Knee Ligaments.

BACKGROUND: There is limited understanding of differences in the composition and structure of ligaments between healthy males and females, and individuals of different ages. Females present higher risk for ligament injuries than males and there are conflicting reports on its cause. This study looks into T1ρ parameters for an explanation as it relates to proteoglycan, collagen, and water content in these tissues. PURPOSE: To investigate gender-related and age-related differences in T1ρ parameters in knee joint ligaments in healthy volunteers using a T1ρ -prepared zero echo-time (ZTE)-based pointwise-encoding time-reduction with radial acquisition (T1ρ -PETRA) sequence. STUDY TYPE: Prospective. POPULATION: The study group consisted of 22 healthy subjects (11 females, ages: 41 ± 18 years, and 11 males, ages: 41 ± 14 years) with no known inflammation, trauma, or pain in the knee joint. FIELD STRENGTH/SEQUENCE: A T1ρ -prepared 3D-PETRA sequence was used to acquire fat-suppressed images with varying spin-lock lengths (TSLs) of the knee joint at 3T. ASSESSMENT: Monoexponential, biexponential, and stretched-exponential 3D-PETRA-T1ρ parameters were measured in the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and patellar tendon (PT) by manually drawing ROIs over the entirety of the tissues. STATISTICAL TESTS: Mann-Whitney U-tests were used to compare 3D-PETRA-T1ρ parameters in the ACL, PCL, and PT between males and females. Spearman correlation coefficients were used to determine the association between age and T1ρ parameters. Statistical significance was defined as P < 0.05. RESULTS: Significant correlations with age were found the three ligaments with most of the measured T1ρ parameters (rs = 0.28-0.74) with the exception of the short fraction in the PCL (P = 0.18), and the short relaxation time in the ACL (P = 0.58) and in the PCL (P = 0.14). DATA CONCLUSION: 3D-PETRA-T1ρ can detect age-related differences in monoexponential, biexponential, and stretched-exponential T1ρ parameters in three ligaments of healthy volunteers, which are thought to be related to changes in tissue composition and structure during the aging process. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Repeatability of Quantitative Knee Cartilage T1 , T2 , and T1ρ Mapping With 3D-MRI Fingerprinting.

BACKGROUND: Three-dimensional MR fingerprinting (3D-MRF) techniques have been recently described for simultaneous multiparametric mapping of knee cartilage. However, investigation of repeatability remains limited. PURPOSE: To assess the intra-day and inter-day repeatabilities of knee cartilage T1 , T2 , and T1ρ maps using a 3D-MRF sequence for simultaneous measurement. STUDY TYPE: Prospective. SUBJECTS: Fourteen healthy subjects (35.4 ± 9.3 years, eight males), scanned on Day 1 and Day 7. FIELD STRENGTH/SEQUENCE: 3 T/3D-MRF, T1 , T2 , and T1ρ maps. ASSESSMENT: The acquisition of 3D-MRF cartilage (simultaneous acquisition of T1 , T2 , and T1ρ maps) were acquired using a dictionary pattern-matching approach. Conventional cartilage T1 , T2 , and T1ρ maps were acquired using variable flip angles and a modified 3D-Turbo-Flash sequence with different echo and spin-lock times, respectively, and were fitted using mono-exponential models. Each sequence was acquired on Day 1 and Day 7 with two scans on each day. STATISTICAL TESTS: The mean and SD for cartilage T1 , T2 , and T1ρ were calculated in five manually segmented regions of interest (ROIs), including lateral femur, lateral tibia, medial femur, medial tibia, and patella cartilages. Intra-subject and inter-subject repeatabilities were assessed using coefficient of variation (CV) and intra-class correlation coefficient (ICC), respectively, on the same day and among different days. Regression and Bland-Altman analysis were performed to compare maps between the conventional and 3D-MRF sequences. RESULTS: The CV in all ROIs was lower than 7.4%, 8.4%, and 7.5% and the ICC was higher than 0.56, 0.51, and 0.52 for cartilage T1 , T2 , and T1ρ , respectively. The MRF results had a good agreement with the conventional methods with a linear regression slope >0.61 and R2 > 0.59. CONCLUSION: The 3D-MRF sequence had high intra-subject and inter-subject repeatabilities for simultaneously measuring knee cartilage T1 , T2 , and T1ρ with good agreement with conventional sequences. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Updates on Compositional MRI Mapping of the Cartilage: Emerging Techniques and Applications.

Osteoarthritis (OA) is a widely occurring degenerative joint disease that is severely debilitating and causes significant socioeconomic burdens to society. Magnetic resonance imaging (MRI) is the preferred imaging modality for the morphological evaluation of cartilage due to its excellent soft tissue contrast and high spatial resolution. However, its utilization typically involves subjective qualitative assessment of cartilage. Compositional MRI, which refers to the quantitative characterization of cartilage using a variety of MRI methods, can provide important information regarding underlying compositional and ultrastructural changes that occur during early OA. Cartilage compositional MRI could serve as early imaging biomarkers for the objective evaluation of cartilage and help drive diagnostics, disease characterization, and response to novel therapies. This review will summarize current and ongoing state-of-the-art cartilage compositional MRI techniques and highlight emerging methods for cartilage compositional MRI including MR fingerprinting, compressed sensing, multiexponential relaxometry, improved and robust radio-frequency pulse sequences, and deep learning-based acquisition, reconstruction, and segmentation. The review will also briefly discuss the current challenges and future directions for adopting these emerging cartilage compositional MRI techniques for use in clinical practice and translational OA research studies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

IL-33/ST2 antagonizes STING signal transduction via autophagy in response to acetaminophen-mediated toxicological immunity.

BACKGROUND: Interleukin-33 (IL-33), defined as "alarming", exert diverse functions through signaling via the suppression of tumorigenicity 2 (ST2). However, the physiological roles of IL-33/ST2 signaling during acetaminophen (APAP)-induced liver injury are still poorly understood by modern medicine (AILI). This research aims to explore the relationship between IL-33/ST2 and stimulator of interferon (IFN) response cGAMP interactor 1 (STING)-mediated signal transduction. METHODS: C57BL/6N mice (WT) and IL-33-deficient mice (KO) were intraperitoneally injected with APAP (250 mg/kg). Recombinant IL-33 (500 ng/mouse) and the cGAS/STING inhibitor RU.521 (200 g/kg) were combined to treat AILI. For mechanistic research in vitro, CRISPR-mediated KD technology, immunoprecipitation, mass spectrometry, and immunofluorescence were utilized. RESULTS: We discovered that IL-33 deficient mice had increased APAP-induced hepatotoxicity, DNA accumulation, and type 1 IFN production. Mechanistic analysis revealed that IL-33/ST2 enhanced the interaction between Beclin-1 and STING, disrupting STING dimerization, IRF3 phosphorylation, nuclear transport, and IFN-1 gene transcription in HepaRG and Huh7 cells. Beclin-1 interacted with the C-terminus of STING, causing Lys338 acetylation and autophagy degradation of STING. ST2 depletion increased STING signal transduction and IFN-1 promoter activity. Surprisingly, the cGAS/STING inhibitor RU.521 and recombinant IL-33 together improved AILI in vivo. CONCLUSIONS: These results shed insight on the potential of inhibiting cGAS/STING as a therapy for AILI and emphasize the crucial role of IL-33/ST2 signaling in the regulation of APAP-induced STING signaling. Video Abstract.

Salipaludibacillus daqingensis sp. nov., a moderately halophilic bacterium isolated from an oilfield.

A novel alkaliphilic, Gram-stain-positive, moderately halophilic, rod-shaped, endospore-forming, motile, facultatively anaerobic bacterium (DQ-9T) was isolated from a sediment sample collected from Daqing oilfield in China, and characterized by a polyphasic taxonomic approach. Strain DQ-9T formed yellow pigment and grew occurred at salinities of 1-12 % (w/v) NaCl (optimum, 8 %) and at 10-40 °C (optimum, 30-35 °C), at pH 7.5-10.5 (optimum, pH 9.0-9.5). It was catalase-positive, but oxidase-negative. Based on the analysis of 16S rRNA gene sequences, DQ-9T was classified into the genus Salipaludibacillus and exhibited the highest similarities (98.37 %) to Salipaludibacillus neizhouensis JSM 071004T. Digital DNA-DNA hybridization and average nucleotide identity values between strain DQ-9T and the most closely related strain, S. neizhouensis DSM 19794T, were determined to be 72.0 and 21.6 %, respectively. The polar lipids were constituted by diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major fatty acids (>5 %) comprised anteiso-C15 : 0, anteiso-C17 : 0, iso-C17 : 0, iso-C15 : 0 and C16 : 0. The cell-wall peptidoglycan contained meso-diaminopimelic acid, and menaquinone-7 was identified as the primary respiratory quinone. The DNA G+C content was 37.5 mol%. Through chemotaxonomic, physiological, and biochemical characterization, strain DQ-9T could be clearly distinguished from the closest Salipaludibacillus species. Based on provided data, strain DQ-9T is proposed to represent a novel species, Salipaludibacillus daqingensis sp. nov., within the genus Salipaludibacillus. The type strain is DQ-9T (=ACCC 60415T=KCTC 33936T).