A comprehensive evaluation of milk protein molecular weight distribution based on exclusion chromatography dataset.

Molecular weight is one of the main characteristic parameters of proteins, which is the basis for the functional properties of milk protein. This research aims at establishing molecular weight distribution pattern of milk protein based on exclusion chromatography. The method selected Na3PO4-Na2SO4 (0.1 M, pH 6.7) buffer as the mobile phase and detected at 220 nm by HPLC-UV. The protein molecular weight distributions were determined and compared for human milk, bovine milk, and infant formula. The proportion of macromolecular proteins is much higher in infant formula compared to human or bovine milk. The protein molecular weights of human and bovine milk are significantly different around 90, 20, 14, and 2 kDa. The results provide holistic compare of bovine milk, human milk, and infant formula through protein molecular distribution. The new evaluation indicators for protein will drive technological simulation of infant formula.

Overlooked encounter process that affects physical behaviors of stabilized nanoscale zero-valent iron during in situ groundwater remediation.

Dynamic encountering between groundwater matrices and nanoscale zero-valent iron (NZVI) injected for in situ subsurface remediation affects NZVI's mobility and has not been well recognized. Polyacrylic acid (PAA)-stabilized NZVI (NZVI-PAA) and Mg(OH)2-coated NZVI (NZVI@Mg(OH)2) were investigated as representative NZVIs stabilized by enhanced electrostatic repulsion and reduced magnetic attraction, respectively. Encounters with divalent cations and humic acid (HA) induced the drastic aggregation and sedimentation (presedimentation) of NZVI-PAA owing to Lewis acid-base interactions and heteroaggregation. In addition, encountered groundwater electrolytes could not effectively provide electrostatic repulsion for NZVI-PAA, resulting in breakthrough ripening dynamics. The presedimentation and ripening behaviors of NZVI-PAA were eliminated and unheeded after mixing the NZVI slurry with groundwater by sonication. In comparison, the encountering process barely impacted NZVI@Mg(OH)2, for which settling was hindered. Although the particle-collector attraction promoted NZVI@Mg(OH)2 adsorption on pristine and hybrid-coated sands, the Langmuirian blocking dynamics of the NZVI@Mg(OH)2 breakthrough demonstrated its high mobility after adsorption sites of sand surface were exhausted. Extended Derjaguin-Landau-Verwey-Overbeek analysis and transport modeling provided insights into overlooked effects of encountering on physical behaviors of different stabilized NZVIs, which should be considered during practical applications under diverse subsurface conditions.

Deriving aquatic PNECs of endocrine disruption effects for PFOS and PFOA by combining species sensitivity weighted distributions and adverse outcome pathway networks.

Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), as emerging endocrine-disrupting chemicals (EDCs), pose adverse effects on aquatic organisms. Conventional ecological risk assessment (ERA) not fully considering the mode of toxicity action of PFOS and PFOA, may result in an underestimation of risks and confuse decision-makers. In the study, we developed species sensitivity weighted distribution (SSWD) models based on adverse outcome pathway (AOP) networks for deriving predicted no-effect concentrations (PNECs). Three kinds of weighting criteria (intraspecies variation, trophic level abundance, and data quality) and weighted log-normal distribution methods were adopted. The developed models considered the inter/intraspecies variation and integrated nontraditional endpoints of endocrine-disrupting effects. The PNECs of endocrine disruption effects were derived as 2.52 µg/L (95% confidence intervals 0.667-9.85 µg/L) for PFOS and 18.7 µg/L (5.40-71.0 µg/L) for PFOA, which were more conservative than those derived from the SSD method and were comparable with the values in the literature based on the chronic toxicity data. For PFOS, the effect of growth and development was the most sensitive; however, for PFOA, the effect of reproduction was the most sensitive in the effects of growth and development, reproduction, biochemistry and genetics, and survival. The endocrine-disrupting effects of PFOS and PFOA are significant and need to be fully recognized in the ERA. This study provided an ERA framework that can improve the ecological relevance and reduce the uncertainty of PNECs of EDCs.

Polystyrene nanoplastics induce glycolipid metabolism disorder via NF-κB and MAPK signaling pathway in mice.

Nanoplastics-induced developmental and reproductive toxicity, neurotoxicity and immunotoxicity are a focus of widespread attention. However, the effects of nanoplastics (NPs) on glycolipid metabolism and the precise underlying mechanisms are unclear at present. Here, we showed that oral administration of polystyrene nanoparticles (PS-NPs) disrupts glycolipid metabolism, with reactive oxygen species (ROS) identified as a potential key signaling molecule. After PS-NPs treatment, excessive production of ROS induced the inflammatory response and activated the antioxidant pathway through nuclear factor-erythroid factor 2-related factor 2. The activation of nuclear factor-κB (NFκB) signaling pathway induced the phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway, which induced the activation of extracellular regulated kinases (ERK) and p38. Constitutive activation of the MAPK signaling proteins induced high continued phosphorylation of insulin receptor substrate-1, in turn, leading to decreased protein kinase B (Akt) activity, which weakened the sensitivity of liver cells to insulin signals and induced insulin resistance. In parallel, phosphorylation of Akt led to loss of control of FoXO1, a key gene of gluconeogenesis, activating transcription of glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (PEPCK) in a manner dependent on PGC1α. Moreover, the activated ERK promoted lipid accumulation through ERK-PPARγ cascades. Therefore, sterol regulatory element-binding protein-1 and levels of its downstream lipogenic enzymes, ACC-1, were up-regulated. Upon treatment with the antioxidant resveratrol, PS-NPs-induced glucose and lipid metabolic disorders were improved by inhibiting ROS-induced activation of NFκB and MAPK signaling pathway in mice. Based on above, PS-NPs exposure disrupts glycolipid metabolism in mice, with ROS identified as a potential key signaling molecule.

Production of the C/TiO2 composite with a high-performance electrochemical property from titanium-rich sludge via in-situ C coating.

Resource recycling from waste-water and sludge is an important part of the 14th Five-Year Plan in China. The emerging titanium-based coagulants have drawn growing attentions due to their strong coagulation capability in water purification and value-added Ti-loaded sludge production. Management and recovery of the high value-added sludge into functional nanomaterials is highly significant for both sludge reduction and environmental remediation. The present study was carried out to investigate the recycle of the coagulated Ti-loaded sludge to produce functional C/TiO2 composites as the anode materials for lithium-ion batteries (LIBs). It is the first time that the application of the Ti-loaded wastewater sludge derived C/TiO2 was evaluated for LIBs. The experimental results showed that the carbon coating through in-situ carbonization of the sludge produced the C/TiO2 composites with a high specific surface area, stable structural integrity, and excellent electrochemical properties that would facilitate Li+ diffusion in long-term LIBs usage. The C/TiO2 composites calcinated from the polytitanium sulfate-coagulated sludge at 800°C (N2) exhibited the best electrochemical performance during the cycling tests (601 mAh/g at 100 mA/g after 200 cycles). The research work demonstrates the promising prospect of the recycle and value-added utilization of the Ti-loaded sludge in the production of high-performance C/TiO2 composites for energy storage applications. This study provides a new way for the management and reuse of Ti-loaded waste-sludge.

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function.

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Cancer stem cells and their niche in cancer progression and therapy.

High recurrence and metastasis rates and poor prognoses are the major challenges of current cancer therapy. Mounting evidence suggests that cancer stem cells (CSCs) play an important role in cancer development, chemoradiotherapy resistance, recurrence, and metastasis. Therefore, targeted CSC therapy has become a new strategy for solving the problems of cancer metastasis and recurrence. Since the properties of CSCs are regulated by the specific tumour microenvironment, the so-called CSC niche, which targets crosstalk between CSCs and their niches, is vital in our pursuit of new therapeutic opportunities to prevent cancer from recurring. In this review, we aim to highlight the factors within the CSC niche that have important roles in regulating CSC properties, including the extracellular matrix (ECM), stromal cells (e.g., associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and mesenchymal stem cells (MSCs)), and physiological changes (e.g., inflammation, hypoxia, and angiogenesis). We also discuss recent progress regarding therapies targeting CSCs and their niche to elucidate developments of more effective therapeutic strategies to eliminate cancer.

Occurrence and Removal of Antibiotic Resistance in Nationwide Hospital Wastewater Deciphered by Metagenomics Approach - China, 2018-2022.

What is already known about this topic?: Hospital wastewater represents a significant conduit for the dissemination of antibiotic resistance genes (ARGs), including those that are of clinical importance. Yet, the variation in antibiotic resistance on a national level, which can be influenced by regional differences, has not been thoroughly elucidated. What is added by this report?: Uniform methodologies were employed to analyze data from various provincial-level administrative divisions in China, aiming to investigate the patterns of antibiotic resistance across these regions. This analysis illuminated the location preferences of clinically ARGs on plasmids. Additionally, our study uncovered regional variations in the presumed bacterial hosts of ARGs at the genus level. What are the implications for public health practice?: This investigation has shed light on the nationwide prevalence of ARGs in hospital wastewater in China, uncovering the significant ecological and public health risks associated with the disposal of such effluents.

Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis.

OBJECTIVE: There are many injectable treatments for knee osteoarthritis with different characteristics and effects, the aim is to understand which one can lead to better and safer results. METHODS: The PRISMA principles were followed when doing the literature search. Web of Science databases, Embase, the Cochrane Library, PubMed, and the Wanfang database were searched to identified randomized controlled trials that assessed the efficacy of corticosteroids (CSC), platelet-rich plasma (PRP), hyaluronic acid (HA), and combination therapy in treating KOA. Risk of bias was assessed using the relevant Cochrane tools (version 1.0). The outcome measure included the visual analog scale (VAS) score, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, and treatment-related adverse events. The network meta-analysis was performed using STATA17 software and a Bayesian stratified random effects model. RESULTS: Network meta-analysis using the Bayesian random-effects model revealed 35 studies with 3104 participants. PRP showed the best WOMAC score at a 3-month follow-up, followed by PRP + HA, HA, placebo, and CSC; PRP + HA scored the highest VAS, followed by PRP, CSC, HA, and placebo. PRP, CSC, HA, and placebo had the highest WOMAC scores six months following treatment; PRP + HA showed the best VAS scores. PRP showed the best WOMAC score at 12 months, followed by PRP + HA, HA, placebo, and CSC; The best VAS score was obtained with PRP, followed by PRP + HA, HA, and CSC. No therapy demonstrated a rise in adverse events linked to the treatment in terms of safety. CONCLUSIONS: The current study found that PRP and PRP + HA were the most successful in improving function and alleviating pain after 3, 6, and 12 months of follow-up. CSC, HA, PRP, and combination therapy did not result in an increase in the incidence of treatment-related side events as compared to placebo.

MicroRNA-155 targets SOCS1 to inhibit osteoclast differentiation during orthodontic tooth movement.

BACKGROUND: MicroRNA-155 (miR-155) is a multifunctional miRNA whose expression is known to be involved in a range of physiological and pathological processes. Its association with several oral diseases has been established. However, the specific role of miR-155 in orthodontic tooth movement remains unclear. In this study, we investigated the impact of miR-155 on osteoclast differentiation and orthodontic tooth movement models, aiming to explore the underlying mechanisms. METHODS: In this experiment, we utilized various agents including miR-155 mimic, miR-155 inhibitor, as well as non-specific sequences (NC mimic & NC inhibitor) to treat murine BMMNCs. Subsequently, osteoclast induction (OC) was carried out to examine the changes in the differentiation ability of monocytes under different conditions. To assess these changes, we employed RT-PCR, Western blotting, and TRAP staining techniques. For the orthodontic tooth movement model in mice, the subjects were divided into two groups: the NaCl group (injected with saline solution) and the miR-155 inhibitor group (injected with AntagomiR-155). We observed the impact of orthodontic tooth movement using stereoscopic microscopy, micro-CT, and HE staining. Furthermore, we performed RT-PCR and Western blotting analyses on the tissues surrounding the moving teeth. Additionally, we employed TargetScan to predict potential target genes of miR-155. RESULTS: During osteoclast induction of BMMNCs, the expression of miR-155 exhibited an inverse correlation with osteoclast-related markers. Overexpression of miR-155 led to a decrease in osteoclast-related indexes, whereas underexpression of miR-155 increased those indexes. In the mouse orthodontic tooth movement model, the rate of tooth movement was enhanced following injection of the miR-155 inhibitor, leading to heightened osteoclast activity. TargetScan analysis identified SOCS1 as a target gene of miR-155. CONCLUSIONS: Our results suggest that miR-155 functions as an inhibitor of osteoclast differentiation, and it appears to regulate osteoclasts during orthodontic tooth movement. The regulatory mechanism of miR-155 in this process involves the targeting of SOCS1.

Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures.

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.

The effect of recasting by mothers with different conversational styles on the communication behavior of autistic children: Lag sequential analysis.

Recasting is the adult rephrasing of a child's immediately preceding utterance. It has been shown to have outstanding effects on promoting language development in autistic children. This study used lag sequential analysis to explore the impact of mothers' conversational styles on the communicative behavior of autistic children when using recasting. This study recruited 30 Chinese autistic children (aged 3-6 years) and their mothers. The utterances of the children and their mothers during 30-min interactions were transcribed, coded, and analyzed. The mothers' conversational styles were determined by the percentages of child-dominant, mother-dominant, and equality styles. The results indicated that mothers' conversational styles were predominantly child-dominant, differing from the expected mother-dominant style that is typical in Eastern cultures and traditions. However, some mothers still demonstrated a significant proportion of mother-dominant style in their conversation, while some exhibited a considerable amount of equality style. Moreover, mothers with a mainly child-dominant style and minimal use of mother-dominant and equality styles used recasting after the child's response, triggering the child to initiate new topics. Mothers with a child-dominant style combined with prominent mother-dominant features implemented untargeted self-recasting, the children did not respond significantly. Mothers with a child-dominant style combined with prominent equality features used recasting after the children responded, initiated, or expanded the conversation, which often facilitated the child's expansion of the conversation. These findings provide suggestions for designing parent-mediated early language interventions for autistic children.

Flexible All-Solid-State Asymmetric Supercapacitors Based on PPy-Decorated SrFeO3-δ Perovskites on Carbon Cloth.

The defective structure and high oxygen vacancy concentration of SrFeO3-δ perovskite enable fast ion-electron transport, but its low conductivity still hinders the high electrochemical performance. Herein, to enhance the conductivity of SrFeO3-δ-based electrodes, polypyrrole-modified SrFeO3-δ perovskite on carbon cloth (PPy@SFO@CC) has been successfully fabricated by electrodeposition of polypyrrole (PPy) on the surface of SFO@CC. The optimal PPy700@SFO@CC electrode exhibits a specific capacitance of 421 F g-1 at 1 A g-1. It was found that the outside PPy layer not only accelerates the electron transport and ion diffusion but also creates more oxygen vacancies in SrFeO3-δ, enhancing the charge storage performance significantly. Moreover, the NiCo2O4@CC//PPy700@SFO@CC device maintains a specific capacitance of 63.6% after 3000 cycles, which is ascribed to the weak adhesion forces between the active materials and carbon cloth. Finally, the all-solid-state flexible supercapacitor NiCo2O4@CC//PPy700@SFO@CC is constructed with PVA-KOH as the solid electrolyte, delivering an energy density of 16.9 W h kg-1 at a power density of 984 W kg-1. The flexible supercapacitor retains 69% of its specific capacitance after 1000 bending and folding times, demonstrating a certain degree of foldability. The present study opens new avenues for perovskite oxide-based flexible all-solid-state supercapacitors.

[Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene].

OBJECTIVE: To explore the genetic basis for a patient with Dilated cardiomyopathy. METHODS: A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG). RESULTS: DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4). CONCLUSION: The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.

The expression of Nrf2 and TLRs in ear effusion in children with different types of otitis media and their relationship with inflammatory factors.

OBJECTIVE: This study aimed to analyze the differences in the expression of Toll-like receptors (TLRs) and nuclear factor erythroid 2-related factor 2 (Nrf2) in ear effusion in children with different types of otitis media (OM), to elaborate the relationship between the expression of TLRs and Nrf2 in ear effusion and the pathogenesis of OM, and to explore the relationship between the two indicators and pro-inflammatory cytokines in children with OM, thereby laying a scientific foundation for revealing the underlying molecular mechanisms of the progression of different types of OM. METHODS: A total of 73 children with OM who were treated in our hospital from March 2019 to July 2021 were selected as the study subjects. By using the cross-sectional investigation method, participants were divided into three groups according to the different pathological types, including the secretory OM group (30 cases), the chronic suppurative OM group (27 cases), and the cystic lesional OM group (16 cases). The levels of Nrf2, TLR2, TLR4 and proinflammatory cytokines [interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), transforming growth factor-ß 1(TGF-ß1), procalcitonin (PCT) and interleukin-1ß (IL-1ß)] were detected in ear effusion of children with different types of OM. Linear regression was used to analyze the correlation between the Nrf2, TLR2 and TLR4 expression levels and pro-inflammatory cytokines in ear effusion. RESULTS: The expression levels of TNF-α and PCT in the ear effusion of the children under 3 years old were significantly higher than that of the children between 3 and 5 years old and that of the children between 6 and 8 years old (all P < 0.001). The mRNA levels of Nrf2, TLR2 and TLR4 in the ear effusion of the children from the chronic suppurative OM group were higher than these from the secretory OM group (P < 0.001, P = 0.008 and P = 0.021). The mRNA levels of Nrf2, TLR2, and TLR4 in the ear effusion of the children from the cystic lesional OM group were higher than those from the chronic suppurative OM group (P < 0.001, P = 0.029 and P = 0.018). A prominent increase in the concentrations of IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß was found in the ear effusion of children from the chronic suppurative OM group compared to these from the secretory OM group (P = 0.021, P = 0.044, P = 0.048, P = 0.004 and P = 0.001). The concentrations of IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß in the ear effusion of the children from the cystic lesional OM group were markedly increased as compared with these from the chronic suppurative OM group (P < 0.001, P = 0.004, P = 0.003, P < 0.001 and P < 0.001). Nrf2, TLR2 and TLR4 were taken as independent variables, and inflammatory indexes, including IFN-γ, TNF-α, TGF-ß1, PCT and IL-1ß were used as dependent variables for the linear regression analysis. The results showed that Nrf2, TLR2 and TLR4 were positively correlated with the secretion levels of pro-inflammatory cytokines after adjusting for age, sex, course and the OM classification (all P < 0.05). CONCLUSION: The expressions of Nrf2, TLR2 and TLR4 in the ear effusion of children with different types of OM gradually increased with the severity of the disease, these were significantly positively correlated with the pro-inflammatory cytokines of the children. Nrf2/TLR signaling pathway maintained chronic inflammation in OM, induced damage of middle ear tissue, and promoted the transition from acute OM to chronic OM.

[Clinical and genetic analysis of a patient with Loeys-Dietz syndrome due to variant of TGFBR2 gene].

OBJECTIVE: To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). METHODS: A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. RESULTS: Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). CONCLUSION: The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.

Placement of peripherally inserted central catheter through upper versus lower limb vein in neonates: A meta-analysis of randomized controlled trials.

AIM: Peripherally inserted central catheter (PICC) is an important treatment for the drug and nutrition administration in neonates. We aimed to evaluate the effects and safety of PICC placement through upper versus lower limb vein in neonates, to provide insights into the clinical PICC nursing care. DESIGN: A meta-analysis. METHODS: We searched the Cochrane Library, Web of Science, PubMed, Science Direct, China national knowledge infrastructure, Wanfang Data Knowledge Service Platform, China Weipu Database, China Biomedical Literature Database for published randomized controlled trials (RCTs) on the placement of PICC via upper limb and lower limb venipuncture. Two reviewers independently evaluated and cross-checked the quality of the included studies in accordance with the quality standards of the Cochrane Manual. We used RevMan 5.3 software for statistical processing. RESULTS: A total of 12 RCTs were included in this meta-analysis. Meta-analysis indicated that compared with upper limb veins, PICC insertion through lower limb veins is beneficial to increase the one-time puncture success rate (relative risk [RR]  =  0.73, 95% confidence interval [CI]: 0.68-0.79) and the indwelling time (mean difference [MD] =  -3.60, 95% CI: -5.35 to -1.86), reduce the operation time (MD =  10.37, 95% CI: 7.48-13.26), estimated bleeding volume (MD =  0.55, 95% CI: 0.34-0.75), incidence of catheter ectopia (RR  =  2.46, 95% CI: 1.81-3.35), PICC-associated infection (RR  =  2.82, 95% CI: 1.65-4.83), exosmosis (RR  =  2.45, 95% CI: 1.49-4.04, p < .001) and phlebitis (RR  =  1.40, 95% CI: 1.03-1.90). No significant difference in the Incidence of catheter obstruction between the upper and lower limb veins (RR  =  1.20, 95% CI: 0.73-1.97, p = .48) was found. PUBLIC CONTRIBUTION: There are certain advantages in neonatal PICC puncture through the lower limb vein. The lower limb vein may be the preferred choice for neonatal PICC puncture.

Molecular characterization of IncFII plasmid carrying blaNDM-5 in a Salmonella enterica serovar Typhimurium ST34 clinical isolate in China.

The detection rate of carbapenem-resistant nontyphoidal Salmonella (NTS) is relatively low. However, carbapenem-sensitive and carbapenem-resistant Salmonella enterica serovar Typhimurium (S. enterica serovar Typhimurium) were isolated from a clinical outpatient within a span of 10 days, named 1104-65 and 1104-75. We aimed to reveal the mechanism of carbapenem resistance in S. enterica serovar Typhimurium isolates in this case. The resistance phenotype of S. enterica serovar Typhimurium was analyzed by the VITEK-2 Compact equipment and Kirby-Bauer disc diffusion method. Whole-genome sequencing was used to analyze the serotype, ST type, genetic relationship, resistance genes, plasmid replicon, the genetic environment of blaNDM-5, and the characteristics of IncFII plasmid carrying blaNDM-5 in S. enterica serovar Typhimurium. The transferability of the IncFII plasmid carrying blaNDM-5 was verified by the conjugation assay and PCR. The serotypes of both NTS are S. enterica serovar Typhimurium, belonging to ST34. Single nucleotide polymorphisms analysis showed that they were the same clone. A conjugative IncFII plasmid pIncFII-NDM5 with transferability was detected in isolate 1104-75, which harboring the blaNDM-5 gene was the primary mechanism responsible for mediating carbapenem resistance in S. enterica serovar Typhimurium. The genetic environment of blaNDM-5 on pIncFII-NDM5 is "IS26-ΔIS3000-IS5-ΔISAba125-blaNDM-5-bleMBL-trpF-dsbC -cutA-IS26", which was confirmed as a novel structure not previously reported in the NCBI database. Although the mechanism is rarely reported in NTS, the prevalence of IncFII plasmid pIncFII-NDM5 will pose a great threat to the clinical treatment of S. enterica serovar Typhimurium. Meanwhile, the coexistence of blaCTX-M-55, qnrS1, blaNDM-5, and mph(A) in S. enterica serovar Typhimurium ST34 warrants additional attention.IMPORTANCEIn this study, an IncFII plasmid pIncFII-NDM5 carrying blaNDM-5 was found in carbapenem-resistant Salmonella enterica serovar Typhimurium (S. enterica serovar Typhimurium), which has conjugative transferability and carried blaNDM-5, bleMBL, mph(A), and blaTEM-1 four resistance genes that can mediate resistance to multiple antibiotics including cephalosporins, beta-lactamase inhibitor combinations, carbapenems, and macrolides. Phylogenetic analysis showed that 1104-65 and 1104-75 were closely related to other S. enterica serovar Typhimurium in this area. The above-mentioned S. enterica serovar Typhimurium chromosome carries blaCTX-M-55, qnrS1, and tet(A) genes, so the antibiotic resistance of isolates will be further enhanced after obtaining the pIncFII_NDM5-like plasmid. Meanwhile, we discovered a novel genetic structure of blaNDM-5 mediated by the IS26 composite transposon, which will expand our understanding of the emergence and spread of carbapenem-resistance genes. Altogether, the presence of the IncFII plasmid pIncFII-NDM5 further underscores the need for vigilant surveillance and appropriate infection control measures to mitigate the impact of carbapenem-resistant S. enterica serovar Typhimurium in clinical settings.

Room-temperature super-elongation in high-entropy alloy nanopillars.

Nanoscale small-volume metallic materials typically exhibit high strengths but often suffer from a lack of tensile ductility due to undesirable premature failure. Here, we report unusual room-temperature uniform elongation up to ~110% at a high flow stress of 0.6-1.0 GPa in single-crystalline <110>-oriented CoCrFeNi high-entropy alloy nanopillars with well-defined geometries. By combining high-resolution microscopy and large-scale atomistic simulations, we reveal that this ultrahigh uniform tensile ductility is attributed to spatial and synergistic coordination of deformation twinning and dislocation slip, which effectively promote deformation delocalization and delay necking failure. These joint and/or sequential activations of the underlying displacive deformation mechanisms originate from chemical compositional heterogeneities at the atomic level and resulting wide variations in generalized stacking fault energy and associated dislocation activities. Our work provides mechanistic insights into superplastic deformations of multiple-principal element alloys at the nanoscale and opens routes for designing nanodevices with high mechanical reliability.

A more accurate relationship between serum androgen and metabolism among healthy, nonobese, reproductive-age women based on liquid chromatography-tandem mass spectrometry.

This study explored a more precise association between androgens and glycolipid metabolism in healthy women of different ages. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio were used as body fat indicators. High-density lipoprotein (HDL), low-density lipoprotein, triglycerides, and total cholesterol were used as lipid markers. Fasting blood glucose (FBG), fasting insulin, and the homeostatic model assessment of insulin resistance were used to assess insulin resistance and glucose metabolism. Liquid chromatography-tandem mass spectrometry was used to measure androgen indicators, including testosterone, sex hormone-binding globulin (SHBG), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). DHEAS levels varied across age groups. Correlation analyses with Spearman's coefficient showed that the free androgen index correlated positively with WC (p = 0.040), FT correlated positively with BMI (p = 0.033) and WC (p = 0.049), SHBG correlated positively with HDL (p = 0.013), and A4 correlated positively with FBG (p = 0.017). Multiple linear regression analysis showed that among healthful women aged 36-40 years, A4 increased with FBG, and SHBG increased with HDL. Even within healthy, nonobese women, lipid and glucose metabolism were robustly correlated with androgens. Yearly metabolic assessments are necessary, particularly for FBG and HDL, since these markers can predict the likelihood of hyperandrogenemia, enabling timely interventions.