Unveiling the effect of Ni on the formation and structure of Earth's inner core.

Ni is the second most abundant element in the Earth's core. Yet, its effects on the inner core's structure and formation process are usually disregarded because of its electronic and size similarity with Fe. Using ab initio molecular dynamics simulations, we find that the bcc phase can spontaneously crystallize in liquid Ni at temperatures above Fe's melting point at inner core pressures. The melting temperature of Ni is shown to be 700 to 800 K higher than that of Fe at 323 to 360 GPa. hcp, bcc, and liquid phase relations differ for Fe and Ni. Ni can be a bcc stabilizer for Fe at high temperatures and inner core pressures. A small amount of Ni can accelerate Fe's crystallization at core pressures. These results suggest that Ni may substantially impact the structure and formation process of the solid inner core.

Accelerating the discovery of novel magnetic materials using machine learning-guided adaptive feedback.

Magnetic materials are essential for energy generation and information devices, and they play an important role in advanced technologies and green energy economies. Currently, the most widely used magnets contain rare earth (RE) elements. An outstanding challenge of notable scientific interest is the discovery and synthesis of novel magnetic materials without RE elements that meet the performance and cost goals for advanced electromagnetic devices. Here, we report our discovery and synthesis of an RE-free magnetic compound, Fe3CoB2, through an efficient feedback framework by integrating machine learning (ML), an adaptive genetic algorithm, first-principles calculations, and experimental synthesis. Magnetic measurements show that Fe3CoB2 exhibits a high magnetic anisotropy (K1 = 1.2 MJ/m3) and saturation magnetic polarization (Js = 1.39 T), which is suitable for RE-free permanent-magnet applications. Our ML-guided approach presents a promising paradigm for efficient materials design and discovery and can also be applied to the search for other functional materials.

A novel antimicrobial peptide S24 combats serious wound infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii.

OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.

Preparation and immunogenicity evaluation of C-HapS-P6 fusion protein vaccine against nontypeable Haemophilus influenzae in mice.

Nontypeable Haemophilus influenzae (NTHi) is the dominant pathogen in several infectious diseases. Currently the use of antibiotics is the main intervention to prevent NTHi infections, however with the emergence of drug resistant strains, it has compromised the treatment of respiratory infections with antibiotics. Therefore there is an urgent need to develop a safe and effective vaccine to prevent NTHi infections. We investigate the potential of C-HapS-P6 fusion protein as a vaccine for treating NTHi in murine models. PGEX-6P2/C-HapS-P6 fusion gene was constructed using overlap extension polymerase chain reaction. The recombined plasmid was transformed into Escherichia coli for protein expression. The mice were subjected to intraperitoneal immunization using purified antigens. Immunoglobulin (Ig) G in serum samples and IgA in nasal and lung lavage fluids were analyzed using enzyme-linked immunosorbent assay. Cytokine release and proliferation capacity of splenic lymphocytes in response to antigens were measured in vitro. The protective effect of the C-HapS-P6 protein against NTHi infection was evaluated by NTHi count and histological examination. The data showed that the C-HapS-P6 fusion protein increased significantly the levels of serum IgG and nasal and lung IgA, and promoted the release of interleukin (IL)-2, interferon-ϒ, IL-4, IL-5, and IL-17 and the proliferation of splenic lymphocytes compared with C-HapS or P6 protein treatment alone. Moreover, C-HapS-P6 effectively reduced the NTHi colonization in the nasopharynx and lungs of mice. In conclusion, our results demonstrated that the C-HapS-P6 fusion protein vaccine can significantly enhance humoral and cell immune responses and effectively prevent against NTHi infection in the respiratory tract in murine models.

Proteomic and metabolomic proof of concept for unified airways in chronic rhinosinusitis and asthma.

BACKGROUND: The pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) with comorbid asthma remains unclear. OBJECTIVE: To assess upper and lower airway unity and identify a possible common pathogenesis in CRSwNP with asthma. METHODS: This study analyzed the expression of proteins and metabolites in nasal lavage fluid cells (NLFCs) and induced sputum cells (ISCs). Differentially expressed proteins and their function-related metabolites in the upper and lower airways of patients having CRSwNP with or without asthma were identified; relevant signaling pathways were analyzed, and key pathway-related proteins were identified. Parallel reaction monitoring was used to verify these target proteins. RESULTS: Protein or metabolite expression between NLFCs and ISCs was highly correlated and conservative on the basis of expression profiles and weighted gene coexpression network analysis. There were 17 differentially coexpressed proteins and their function-related 13 metabolites that were identified in the NLFCs and ISCs of CRSwNP, whereas 11 proteins and 11 metabolites were identified in CRSwNP with asthma. An asthma pathway was involved in the copathogenesis of upper and lower airways in whether CRSwNP or CRSwNP with asthma. The asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase, as the core of the protein-metabolism interaction networks between the upper and lower airways, were both highly coexpressed in NLFCs and ISCs in patients having either CRSwNP or CRSwNP with asthma by parallel reaction monitoring validation. CONCLUSION: Proteomics and metabolomics reveal upper and lower airway unity. Asthma pathway-related proteins proteoglycan 2 and eosinophil peroxidase from the upper airway could be used to assess the potential risk of lower airway dysfunction in CRSwNP.

Structure, bonding and electronic characteristics of amorphous Se.

Ovonic threshold switching (OTS) selectors can effectively improve the storage density and suppress the leakage current of advanced phase-change memory devices. As a prototypical OTS material, amorphous GeSe is widely investigated. But the attention paid to amorphous Se (i.e., the functional constituent in amorphous GeSe) has been very limited up to now. Here we have explored the structure, bonding and electronic characteristics of amorphous Se using ab initio molecular dynamics simulations. The results reveal that the Se atoms in amorphous Se tend to form 2-coordinated configurations, and they connect with each other to form long chains. The fraction of the vibrational density of state located in the high frequency range is relatively large, and the formation energy of the Se-Se bond is as large as 4.44 eV, hinting that the Se-Se bonds in chains possess high stability. In addition, the mid-gap state related to the OTS behavior is also found in amorphous Se despite the small proportion. Our findings enrich the knowledge of amorphous Se, which aids the applications of Se-based OTS selectors.

Discovery of a stilbenoid-flavanone hybrid as an antitumor Wnt/ß-catenin signaling pathway inhibitor.

A series of designed stilbenoid-flavanone hybrids featuring sp3-hybridized C2 and C3 atoms of C-ring was evaluated against colorectal cancers presented compounds 4, 17, and 20 as the most potential compounds among explored compounds. Evaluation of the anticancer activity spectrum of compounds 4, 17, and 20 against diverse solid tumors presented compounds 17 and 20 with interesting anticancer spectrum. The potencies of compounds 17 and 20 were assessed in comparison with FDA-approved anticancer drugs. Compound 17 was the, in general, the most potent showing low micromolar GI50 values that were more potent than the standard FDA-approved drugs against several solid tumors including colon, brain, skin, renal, prostate and breast tumors. Compound 17 was subjected for evaluation against normal cell lines and was subjected to a mechanism study in HCT116 colon cancer cells which presented it as an inhibitor of Wnt signaling pathway triggering G2/M cell cycle arrest though activation of p53-p21 pathway as well as intrinsic and extrinsic apoptotic death of colon cancer cells. Compound 17 might be a candidate for further development against diverse solid tumors including colon cancer.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Changes in the correlation between substantia nigra hyperechogenicity area and Parkinson's disease severity at different Hoehn and Yahr stages.

BACKGROUND: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. METHODS: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. RESULTS: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. CONCLUSIONS: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

Mapping of lymph node metastasis from esophageal squamous cell carcinoma after neoadjuvant treatment: a prospective analysis from a high-volume institution in China.

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

Different Dosages of Progesterone in Luteal Phase Support Reflect Varying Endometrial microRNA Expression in Frozen Embryo Transfer Cycles.

Despite serum progesterone being a widely accepted method for luteal phase support during embryo transfer cycles, debates persist regarding the optimal strategy for guiding clinical decisions on progesterone dosages to maximize reproductive outcomes. This retrospective study explored the utility of microRNA (miRNA) biomarkers in guiding personalized progesterone dosage adjustments for frozen embryo transfer (FET) cycles in 22 in vitro fertilization (IVF) patients undergoing hormone replacement therapy. Utilizing MIRA, an miRNA-based endometrial receptivity test, we analyzed patients' miRNA expression profiles before and after progesterone dosage adjustments to determine suitable dosages and assess endometrial status. Despite patients receiving identical progesterone dosages, variations in miRNA profiles were observed in the initial cycle, and all patients presented a displaced window of implantation. Following dosage adjustments based on their miRNA profiles, 91% of patients successfully transitioned their endometrium towards the receptive stages. However, two patients continued to exhibit persistent displaced receptivity despite the adjustments. Given the evident variation in endometrial status and serum progesterone levels among individuals, analyzing miRNA expression profiles may address the challenge of inter-personal variation in serum progesterone levels, to deliver more personalized dosage adjustments and facilitate personalized luteal phase support in IVF.

Fucoxanthin Induces Ferroptosis in Cancer Cells via Downregulation of the Nrf2/HO-1/GPX4 Pathway.

This study investigated the mechanism by which fucoxanthin acts as a novel ferroptosis inducer to inhibit tongue cancer. The MTT assay was used to detect the inhibitory effects of fucoxanthin on SCC-25 human tongue squamous carcinoma cells. The levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and total iron were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to assess glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor 2 (Nrf2), Keap1, solute carrier family 7 member 11 (SLC7A11), transferrin receptor protein 1 (TFR1), p53, and heme oxygenase 1 (HO-1) expression. Molecular docking was performed to validate interactions. Compared with the control group, the activity of fucoxanthin-treated SCC-25 cells significantly decreased in a dose- and time-dependent manner. The levels of MMP, GSH, and SOD significantly decreased in fucoxanthin-treated SCC-25 cells; the levels of ROS, MDA, and total iron significantly increased. mRNA and protein expression levels of Keap1, GPX4, Nrf2, and HO-1 in fucoxanthin-treated cells were significantly decreased, whereas levels of TFR1 and p53 were significantly increased, in a concentration-dependent manner. Molecular docking analysis revealed that binding free energies of fucoxanthin with p53, SLC7A11, GPX4, Nrf2, Keap1, HO-1, and TFR1 were below -5 kcal/mol, primarily based on active site hydrogen bonding. Our findings suggest that fucoxanthin can induce ferroptosis in SCC-25 cells, highlighting its potential as a treatment for tongue cancer.

Possible enrichment process of Cd in the Se-rich soil area of Lanshan District, Shandong Province, China.

High cadmium (Cd) concentrations widely occured in selenium (Se)-rich soils, which has been an important obstacle in the usage of Se-rich soils. There is still no special information detailing the enrichment process and mechanism of Cd in Se-rich soils. 4474 soils and 21 rocks in Lanshan District were sampled to detect its enrichment process. The surface soils have Cd concentrations of 0.01-9.41 mg·kg-1 (an average of 0.16 mg·kg-1). The soil Cd concentrations were significantly correlated with soil Se concentrations. The relatively higher-Cd surface soils are distributed in Lower-middle Ordovician carbonate areas with Se-rich soils and Quaternary areas with typical anthropic activities. Surface soils in Ordovician carbonate area have the highest Cd concentrations. Soil Cd concentrations are significantly correlated with sulfophil elements (Zinc (Zn), Copper (Cu), Molybdenum (Mo), Lead (Pb) and Arsenic (As) etc.), Ca (Calcium) concentrations and soil organic carbon (SOC). The soil and rock samples from different geological units also confirmed soil Cd concentrations developing from Ordovician carbonates were higher than those from other rocks. The results indicate the soil Cd concentrations were the complex consequences of bedrock, soil-forming processes and anthropogenic activities. Higher Ca concentrations and more reduction environments result in high-Cd bedrock. CaCO3 leaching and alkaline pH, which are the special soil-forming process of carbonates, enrich Cd in soils. Agricultural and industrial activities also affect soil Cd concentrations. An enrichment model of Cd in Se-rich soils is forwarded.

[Cloning and functional characterization of oxidosqualene cyclase gene for α-amyrin synthesis].

Ursolic acid has gradually attracted much attention due to its unique pharmacological activities and valuable market value in recent years. Currently, ursolic acid is mostly extracted from loquat leaves, but the plant extraction method has low yield and high cost, and chemical synthesis is not readily available, so the biosynthesis method provides a new source for ursolic acid. α-amyrin acts as the main precursor for the synthesis of ursolic acid, and its yield is positively correlated with ursolic acid yield. Oxidosqualene cyclase(OSC) belongs to a multigene family which can catalyze the common precursor 2,3-oxidosqualene to generate different types of triterpene backbones, and plays a decisive role in the synthesis of triterpenoids. However, there are fewer reported key genes catalyzing the synthesis of α-amyrin in medicinal plants, and the yield and proportion of α-amyrin in the catalyzed products have always been a focus of research. In this study, ItOSC2, MdOSC1, AaOSC2 and CrAS, four enzymes capable of catalyzing the production of α-amyrin from 2,3-oxidosqualene, were cloned from Iris tectorum, Malus domestica, Artemisia annua and Catharanthus roseus, subject to sequence alignment and phylogenetic tree analyses, and transformed into Saccharomyces cerevisiae as plasmids. After 7 days of fermentation, the yield and proportions of α-amyrin, ß-amyrin and ergosterol were measured. Finally, AaOSC2 with the best ability to catalyze the generation of α-amyrin was filtered out, providing a key gene element for the later construction of engineered yeast strains with high production of α-amyrin and ursolic acid.

[Role of NLRP3 inflammasome in prevention and treatment of cognitive impairment-related diseases and traditional Chinese medicine intervention: a review].

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.

Selective Construction and Structural Transformation of Homogeneous Linear Metalla[4]catenane and Metalla[2]catenane Assemblies.

Although the synthesis of mechanically interlocked molecules has been extensively researched, selectively constructing homogeneous linear [4]catenanes remains a formidable challenge. Here, we selectively constructed a homogeneous linear metalla[4]catenane in a one-step process through the coordination-driven self-assembly of a bidentate benzothiadiazole derivative ligand and a binuclear half-sandwich rhodium precursor. The formation of metalla[4]catenanes was facilitated by cooperative interactions between strong sandwich-type π-π stacking and non-classical hydrogen bonds between the components. Moreover, by modulating the aromatic substituents on the binuclear precursor, two homogeneous metalla[2]catenanes were obtained. The molecular structures of these metallacatenanes were unambiguously characterized by single-crystal X-ray diffraction analysis. Additionally, reversible structural transformation between metal-catenanes and the corresponding metallarectangles could be achieved by altering their concentration, as confirmed by mass spectrometry and NMR spectroscopy studies.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Selective Chemical Labeling Strategy for Oligonucleotides Determination: A First Application to Full-Range Profiling of Transfer RNA Modifications.

To date, the extremely high polarity and poor signal intensity of macromolecular nucleic acids are greatly impeding the progress of mass spectrometry technology in the quality control of nucleic acid drugs and the characterization of DNA oxidation and RNA modifications. We recently described a general N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) labeling method for oligonucleotide determination and applied it to the full-range profiling of tRNA in vitro and in vivo studies for the first time. The primary advantages of this method include strong retention, no observable byproducts, predictable and easily interpreted MS2 data, and the circumvention of instrument harmful reagents that were necessary in previous methods. Selective labeling of N-(tert-butyldimethylsilyl)-N-methyl-trifluoroacetamide to the terminal phosphate groups of oligonucleotides endows it broadly applicable for DNA/RNA profiling. Moreover, the improvement of sequence coverage was achieved in yeast tRNAphe(GAA) analysis owing to this method's good detection capability of 1-12 nucleotides in length. We also extended this strategy to determine the abundance of modified bases and discover new modifications via digesting RNA into single-nucleotide products, promoting the comprehensive mapping of RNA. The easy availability of derivatization reagent and the simple, rapid one-step reaction render it easy to operate for researchers. When applied in characterizing tRNAs in HepG2 cells and rats with nonalcoholic fatty liver disease, a fragment of U[m1G][m2G], specific for tRNAAsn(QUU) in cells, was significantly upregulated, indicating a possible clue to nonalcoholic fatty liver disease pathogenesis.

Facile Access to Fabricate Carbon Dots and Perspective of Large-Scale Applications.

Carbon dots (CDs), fluorescent carbon nanoparticles with particle sizes < 10 nm, are constantly being developed for potential large-scale applications. Recently, methods allow CD synthesis to be carried out on large-scale preparation in a controlled fashion are potentially important for multiple disciplines, including bottom-up strategy, top-down method. In this review, the recent progresses in the research of the methods for large-scale production of CDs and their functionalization are summarized. Especially, the methods of CD synthesis, such as large-scale preparation, hydrothermal/solvothermal, microwave-assisted, magnetic hyperthermia microfluidic and other methods, along with functionalization of CDs, are summarized in detail. By promising applications of CDs, there are three aspects have been already reported, such as enhancing mechanical properties, flame retardancy, and energy storage. Also, future development of CDs is prospected.

Deep stratification by transcriptome molecular characters for precision treatment of patients with systemic lupus erythematosus.

OBJECTIVES: To leverage the high clinical heterogeneity of systemic lupus erythematosus (SLE), we developed and validated a new stratification scheme by integrating genome-scale transcriptomic profiles to identify patient subtypes sharing similar transcriptomic markers and drug targets. METHODS: A normalized compendium of transcription profiles was created from peripheral blood mononuclear cells (PBMCs) of 1046 SLE patients and 86 healthy controls (HCs), covering an intersection of 13 689 genes from six microarray datasets. Upregulated differentially expressed genes were subjected to functional and network analysis in which samples were grouped using unsupervised clustering to identify patient subtypes. Then, clustering stability was evaluated by the stratification of six integrated RNA-sequencing datasets using the same method. Finally, the Xgboost classifier was applied to the independent datasets to identify factors associated with treatment outcomes. RESULTS: Based on 278 upregulated DEGs of the transcript profiles, SLE patients were classified into three subtypes (subtype A-C) each with distinct molecular and cellular signatures. Neutrophil activation-related pathways were markedly activated in subtype A (named NE-driving), whereas lymphocyte and IFN-related pathways were more enriched in subtype B (IFN-driving). As the most severe subtype, subtype C [NE-IFN-dual-driving (Dual-driving)] shared functional mechanisms with both NE-driving and IFN-driving, which was closely associated with clinical features and could be used to predict the responses of treatment. CONCLUSION: We developed the largest cohesive SLE transcriptomic compendium for deep stratification using the most comprehensive microarray and RNA sequencing datasets to date. This result could guide future design of molecular diagnosis and the development of stratified therapy for SLE patients.