Gaussian filter facilitated deep learning-based architecture for accurate and efficient liver tumor segmentation for radiation therapy.

Purpose: Addressing the challenges of unclear tumor boundaries and the confusion between cysts and tumors in liver tumor segmentation, this study aims to develop an auto-segmentation method utilizing Gaussian filter with the nnUNet architecture to effectively distinguish between tumors and cysts, enhancing the accuracy of liver tumor auto-segmentation. Methods: Firstly, 130 cases of liver tumorsegmentation challenge 2017 (LiTS2017) were used for training and validating nnU-Net-based auto-segmentation model. Then, 14 cases of 3D-IRCADb dataset and 25 liver cancer cases retrospectively collected in our hospital were used for testing. The dice similarity coefficient (DSC) was used to evaluate the accuracy of auto-segmentation model by comparing with manual contours. Results: The nnU-Net achieved an average DSC value of 0.86 for validation set (20 LiTS cases) and 0.82 for public testing set (14 3D-IRCADb cases). For clinical testing set, the standalone nnU-Net model achieved an average DSC value of 0.75, which increased to 0.81 after post-processing with the Gaussian filter (P<0.05), demonstrating its effectiveness in mitigating the influence of liver cysts on liver tumor segmentation. Conclusion: Experiments show that Gaussian filter is beneficial to improve the accuracy of liver tumor segmentation in clinic.

Skin microbiome profiling reveals the crucial role of microbial metabolites in anti-photoaging.

BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear. OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome. METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction. RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1ß and IL-6. CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.

Easily misdiagnosed X-linked adrenoleukodystrophy.

BACKGROUND: Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison's-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison's disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD. METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics. RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison's disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison's-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum. CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison's disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison's-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.

Electronic Structure Modification of MnO2 Nanosheet Arrays with Enhanced Water Oxidation Activity and Stability by Nitrogen Plasma.

The strategic design of catalysts for the oxygen evolution reaction (OER) is crucial in tackling the substantial energy demands associated with hydrogen production in electrolytic water splitting. Despite extensive research on birnessite (δ-MnO2) manganese oxides to enhance catalytic activity by modulating Mn3+ species, the ongoing challenge is to simultaneously stabilize Mn3+ while improving overall activity. Herein, oxygen (O) vacancies and nitrogen (N) doping have been simultaneously introduced into the MnO2 through a simple nitrogen plasma approach, resulting in efficient OER performance. The optimized N-MnO2v electrocatalyst exhibits outstanding OER activity in alkaline electrolyte, reducing the overpotential by nearly 160 mV compared to pure pristine MnO2 (from 476 to 312 mV) at 10 mA cm-2, and a small Tafel slope of 89 mV dec-1. Moreover, it demonstrates excellent durability over a 122 h stability test. The introduction of O vacancies and incorporation of N not only fine-tune the electronic structure of MnO2, increasing the Mn3+ content to enhance overall activity, but also play a crucial role in stabilizing Mn3+, thereby leading to exceptional stability over time. Subsequently, density functional theory calculations validate the optimized electronic structure of MnO2 achieved through the two engineering methods, effectively lowering the intermediate adsorption free energy barrier. Our synergistic approach, utilizing nitrogen plasma treatment, opens a pathway to concurrently enhance the activity and stability of OER electrocatalysts, applicable not only to Mn-based but also to other transition metal oxides.

A precise microdissection strategy enabled spatial heterogeneity analysis on the targeted region of formalin-fixed paraffin-embedded tissues.

In recent years, the development of spatial transcriptomic technologies has enabled us to gain an in-depth understanding of the spatial heterogeneity of gene expression in biological tissues. However, a simple and efficient tool is required to analyze multiple spatial targets, such as mRNAs, miRNAs, or genetic mutations, at high resolution in formalin-fixed paraffin-embedded (FFPE) tissue sections. In this study, we developed hydrogel pathological sectioning coupled with the previously reported Sampling Junior instrument (HPSJ) to assess the spatial heterogeneity of multiple targets in FFPE sections at a scale of 180 µm. The HPSJ platform was used to demonstrate the spatial heterogeneity of 9 ferroptosis-related genes (TFRC, NCOA4, FTH1, ACSL4, LPCAT3, ALOX12, SLC7A11, GLS2, and GPX4) and 2 miRNAs (miR-185-5p and miR522) in FFPE tissue samples from patients with triple-negative breast cancer (TNBC). The results validated the significant heterogeneity of ferroptosis-related mRNAs and miRNAs. In addition, HPSJ confirmed the spatial heterogeneity of the L858R mutation in 7 operation-sourced and 4 needle-biopsy-sourced FFPE samples from patients with lung adenocarcinoma (LUAD). The successful detection of clinical FFPE samples indicates that HPSJ is a precise, high-throughput, cost-effective, and universal platform for analyzing spatial heterogeneity, which is beneficial for elucidating the mechanisms underlying drug resistance and guiding the prescription of mutant-targeted drugs in patients with tumors.

The supramolecular synthon behavior within cocrystals of pyrazinamide and alkyl dicarboxylic acids: A perspective from terahertz spectroscopy and quantum chemical calculation.

Pyrazinamide (PZA) is a widely-used anti-tuberculosis pharmaceutical, but its poor solubility prompts us to optimize pharmaceutical performance. Cocrystallization is a promising technique to improve physiochemical properties of active pharmaceutical ingredient (API) by connecting it with cocrystal former (CCF) via intermolecular interactions. Even though a series of alkyl dicarboxylic acids are employed to form cocrystal structures, systematic understanding on the role of intermolecular interactions is still missing. Therefore, terahertz (THz) spectroscopy and quantum chemical calculation are combined to elucidate the behavior of ubiquitous supramolecular synthons, such as hetero-synthons of acid-pyrazine, acid-amide and homo-synthon of amide-amide, from energy's view. Potential energy is calculated to differentiate the stability within polymorphs of PZA-MA cocrystal and free energy is evaluated to compare the solubility of PZA-CCF cocrystals respectively. With regard to vibrational energy, THz spectral fingerprints are theoretically assigned to specific vibrations and attributed to the flexibility deformation of supramolecular synthons based on oscillation theory, where stretching and twisting modes dominate the collective vibrational behavior. It provides a promising tool to evaluate cocrystal performance from its driving force and insightful guidance to discover new pharmaceutical cocrystals.

A risk prediction model of gestational diabetes mellitus based on traditional and genetic factors.

BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication during pregnancy. We aimed to evaluate a risk prediction model of GDM based on traditional and genetic factors. METHODS: A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to gather general data. Serum test results were collected from the laboratory information system. Independent risk factors for GDM were identified using univariate and multivariate logistic regression analyses. A GDM risk prediction model was constructed and evaluated with the Hosmer-Lemeshow goodness-of-fit test, goodness-of-fit calibration plot, receiver operating characteristic curve and area under the curve. RESULTS: Among traditional factors, age ≥30 years, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms (SNPs) (rs2779116, rs5215, rs11605924, rs7072268, rs7172432, rs10811661, rs2191349, rs10830963, rs174550, rs13266634 and rs11071657) were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. CONCLUSIONS: Both genetic and traditional factors contribute to the risk of GDM in women, operating through diverse mechanisms. Strengthening the risk prediction of SNPs for postpartum DM among women with GDM history is crucial for maternal and child health protection.

We aimed to evaluate a risk prediction model of gestational diabetes mellitus (GDM) based on traditional and genetic factors. A total of 2744 eligible pregnant women were included. Face-to-face questionnaire surveys were conducted to collect general data. Among traditional factors, age ≥30 years old, family history, GDM history, impaired glucose tolerance history, systolic blood pressure ≥116.22 mmHg, diastolic blood pressure ≥74.52 mmHg, fasting plasma glucose ≥5.0 mmol/L, 1-hour postprandial blood glucose ≥8.8 mmol/L, 2-h postprandial blood glucose ≥7.9 mmol/L, total cholesterol ≥4.50 mmol/L, low-density lipoprotein ≥2.09 mmol/L and insulin ≥11.5 mIU/L were independent risk factors for GDM. Among genetic factors, 11 single nucleotide polymorphisms were identified as potential predictors of the risk of postpartum DM among women with GDM history, collectively accounting for 3.6% of the genetic risk. Both genetic and traditional factors increase the risk of GDM in women.

Butyrate promotes visceral hypersensitivity in IBS model via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.

Emerging evidence indicates that gut dysbiosis is involved in the pathogenesis of visceral hypersensitivity (VH). However, how gut microbiota contributes to the development of VH is unknown. Here, we sought to examine the signal transduction pathways from gut to dorsal root ganglion (DRG) responsible for this. Therefore, abdominal withdrawal reflex (AWR) scores, fecal output, fecal water content, and total gastrointestinal transit time (TGITT) were assessed in Con rats, VH rats, rats treated with NaB, and VH rats treated with VSL#3. Fecal microbiota and its metabolite (short-chain fatty acids, SCFAs), mast cell degranulation in colon, lincRNA-01028, miR-143, and protease kinase C (PKC) and TRPV1 expression in DRGs were further detected. VH rats showed an increased fecal water content, a shortened TGITT, an increased abundance of Clostridium sensu stricto 1 and increased butyrate in fecal samples, an increased mast cell degranulation, an increased expression of lincRNA-01028, PKC, and TRPV1, and a decreased expression of miR-143 in DRGs compared with control rats, which could be restored by the application of probiotic VSL#3. The above-mentioned detection in rats treated with butyrate was similar to that of VH rats. We further confirm whether butyrate sensitized DRG neurons by a lincRNA-01028, miR-143, and PKC-dependent mechanism via mast cell in vitro. In co-cultures, MCs treated with butyrate elicited a higher TRPV1 current, a higher expression of lincRNA-01028, PKC, and a lower expression of miR-143 in DRG neurons, which could be inhibited by a lincRNA-01028 inhibitor. These findings indicate that butyrate promotes visceral hypersensitivity via mast cell-derived DRG neuron lincRNA-01028-PKC-TRPV1 pathway.IMPORTANCEIrritable bowel syndrome (IBS), characterized by visceral hypersensitivity, is a common gastrointestinal dysfunction syndrome. Although the gut microbiota plays a role in the pathogenesis and treatment of irritable bowel syndrome (IBS), the possible underlying mechanisms are unclear. Therefore, it is of critical importance to determine the signal transduction pathways from gut to DRG responsible for this in vitro and in vivo assay. This study demonstrated that butyrate sensitized TRPV1 in DRG neurons via mast cells in vivo and in vitro by a lincRNA-01028, miR-143, and PKC-dependent mechanism. VH rats similarly showed an increased abundance of Clostridium sensu stricto 1, an increased fecal butyrate, an increased mast cell degranulation, and increased expression of TRPV1 compared with control rats, which could be restored by the application of VSL#3. In conclusion, butyrate produced by the altered intestinal microbiota is associated with increased VH.

Structurally and mechanically tuned macroporous hydrogels for scalable mesenchymal stem cell-extracellular matrix spheroid production.

Mesenchymal stem cells (MSCs) are essential in regenerative medicine. However, conventional expansion and harvesting methods often fail to maintain the essential extracellular matrix (ECM) components, which are crucial for their functionality and efficacy in therapeutic applications. Here, we introduce a bone marrow-inspired macroporous hydrogel designed for the large-scale production of MSC-ECM spheroids. Through a soft-templating approach leveraging liquid-liquid phase separation, we engineer macroporous hydrogels with customizable features, including pore size, stiffness, bioactive ligand distribution, and enzyme-responsive degradability. These tailored environments are conducive to optimal MSC proliferation and ease of harvesting. We find that soft hydrogels enhance mechanotransduction in MSCs, establishing a standard for hydrogel-based 3D cell culture. Within these hydrogels, MSCs exist as both cohesive spheroids, preserving their innate vitality, and as migrating entities that actively secrete functional ECM proteins. Additionally, we also introduce a gentle, enzymatic harvesting method that breaks down the hydrogels, allowing MSCs and secreted ECM to naturally form MSC-ECM spheroids. These spheroids display heightened stemness and differentiation capacity, mirroring the benefits of a native ECM milieu. Our research underscores the significance of sophisticated materials design in nurturing distinct MSC subpopulations, facilitating the generation of MSC-ECM spheroids with enhanced therapeutic potential.

Types of short video addiction among college freshmen: Effects on career adaptability, insomnia, and depressive symptoms.

This study investigated the effects of different types of short video addiction on social adaptation. The aim of this study was to identify the various types of short video addiction among freshmen and the correlations with career adaptability, insomnia, and depressive symptoms. We recruited 931 freshmen and used latent profile analysis to classify participants based on different characteristics of short video addiction. Based on the results of a short video addiction questionnaire, participants were found to exhibit distinct answer patterns, categorized into five types. Class 1 exhibited minimal signs of addiction. Class 2 displayed fluctuations with stronger tendencies towards withdrawal or escape. Class 3 demonstrated a moderate inability to control cravings for short videos. Class 4 showed fluctuations but with less anxiety and feelings of lost. Finally, Class 5 presented the most pronounced symptoms of short video addiction. Freshmen with varying degrees of short video addiction exhibited significant differences in career adaptability, sleep quality, and depressive symptoms. Class 1 students showed strong career adaptability and sound sleep, whereas Class 5 students had the highest depression rates. Overall, our findings suggest that the characteristics of short video addiction in first-year students also indicate poor social adaptation, which is mainly manifested as weak career adaptability, decreased sleep quality, and depressive symptoms. One way to guide first-year students to adapt to campus life is for educators to provide timely interventions for students with severe short video addiction.

Metabolic health and genetic predisposition in inflammatory bowel disease: Insights from a prospective cohort study.

BACKGROUND: Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. METHOD: This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. RESULTS: During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. CONCLUSION: Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.

The role of N-acetylcysteine on adhesion and biofilm formation of Candida parapsilosis isolated from catheter-related candidemia.

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.

Long-term blood pressure variability and risk of cardiovascular diseases in populations with different blood pressure status: an ambispective cohort study.

OBJECTIVE: We aimed to investigate the correlation between long-term blood pressure variability (BPV) and the risk of cardiovascular diseases (CVDs) among population with different blood pressure statuses (normotension, well-controlled hypertension, and uncontrolled hypertension). METHODS: In this ambispective cohort study, CVD-free residents aged over 50 years were consecutively enrolled from two community health service centers (CHCs) in Tianjin, China from April 2017 to May 2017. Information on blood pressure was retrospectively extracted from electronic medical records of CHCs between January 2010 and May 2017, and the occurrence of new-onset CVDs was prospectively observed during follow-up until September 2019. Long-term variation of SBP and DBP was assessed using four indicators: SD, coefficient of variation (CV), average successive variability (ASV), and average real variability (ARV). Cox proportional hazards regression model was developed to identify the potential impact of BPV on the incidence of CVDs. The receiver operating characteristic curve (ROC) was utilized to evaluate the predictive value of BPV indicators for the occurrence of CVDs. RESULTS: Of 1275 participants included, 412 (32.3%) experienced new CVD events during the median 7.7 years of follow-up, with an incidence density of 499/10 000 person-year in the whole cohort. Cox regression analysis revealed that almost all SBP and DBP variability indicators (except for SBP-SD) were significantly related to the risk of CVDs, especially among individuals with well-controlled hypertension. A trend toward an increased risk of CVDs across BPV quartiles was also observed. Moderate predictive abilities of BPV were observed, with the area under ROC curves ranging between 0.649 and 0.736. For SBP variability, SD had the lowest predictive ability, whereas for DBP variability, ARV had the lowest predictive ability. No significant association of CVDs with SBP-SD was found in all analyses, no matter as a continuous or categorical variable. CONCLUSION: Elevated long-term BPV is associated with an increased risk of CVDs, especially among individuals with well-controlled hypertension. CV and ASV had higher predictive values than SD and ARV.

Eye of the beholder: Neural synchrony of dynamically changing relations between parent praise and child affect.

In this study, we aimed to determine the role of parental praise and child affect in the neural processes underlying parent-child interactions, utilizing functional near-infrared spectroscopy (fNIRS) hyperscanning. We characterized the dynamic changes in interpersonal neural synchrony (INS) between parents and children (4-6 years old, n = 40 dyads) during a cognitively challenging task. We then examined how changes in parent-child INS are influenced by parental feedback and child affect. Parent-child INS showed a quadratic change over time, indicating a decelerated decline during the interaction period. The relationship of parental praise, in the form of positive feedback, to change in INS was contingent upon the child's positive affect during the task. The highest levels of INS were observed when praise was present and child affect was positive. The left temporo-parietal regions of the child and the right dorsolateral prefrontal and right temporo-parietal regions of the parent demonstrated the strongest INS. The dynamic change in INS during the interaction was associated with children's independent performance on a standardized test of visuospatial processing. This research, leveraging fNIRS hyperscanning, elucidates the neural dynamics underlying the interaction between parent praise and child positive affect, thereby contributing to our broader understanding of parent-child dynamics. RESEARCH HIGHLIGHTS: The level of interpersonal neural synchrony between parents and children dynamically varies during a cognitively challenging (tangram) task. The left temporo-parietal regions of the child and the right dorsolateral prefrontal and right temporo-parietal regions of the parent demonstrate the strongest parent-child neural synchrony. The relationship between parental praise (positive feedback) and parent-child neural synchrony is contingent upon child positive affect during the task. Change in parent-child neural synchrony relates to children's performance on an independent visuospatial processing measure.

Relevance of genetic causes and environmental adaptation of Cronobacter spp. isolated from infant and follow-up formula production factories and retailed products in China: A 7-year period of continuous surveillance based on genome-wide analysis.

The possible contamination routes, environmental adaptation, and genetic basis of Cronobacter spp. in infant and follow-up formula production factories and retailed products in mainland China have been determined by laboratory studies and whole-genome comparative analysis in a 7-year nationwide continuous surveillance spanning from 2012 to 2018. The 2-year continuous multicenter surveillance of the production process (conducted in 2013 and 2014) revealed that the source of Cronobacter spp. in the dry-blending process was the raw dry ingredients and manufacturing environment (particularly in the vibro sieve and vacuum cleaner), while in the combined process, the main contamination source was identified as the packing room. It is important to note that, according to the contamination control knowledge obtained from the production process surveillance, the contamination rate of retail powdered infant formula (PIF) and follow-up formula (FUF) products in China decreased significantly from 2016 onward, after improving the hygiene management practices in factories. The prevalence of Cronobacter spp. in retailed PIF and FUF in China in 2018 was dramatically reduced from 1.55 % (61/3925, in 2012) to an average as low as 0.17 % (13/7655 in 2018). Phenotype determination and genomic analysis were performed on a total of 90 Cronobacter spp. isolates obtained from the surveillance. Of the 90 isolates, only two showed resistance to either cefazolin or cefoxitin. The multilocus sequence typing results revealed that C. sakazakii sequence type 1 (ST1), ST37, and C. malonaticus ST7 were the dominant sequence types (STs) collected from the production factories, while C. sakazakii ST1, ST4, ST64, and ST8 were the main STs detected in the retailed PIF and FUF nationwide. One C. sakazakii ST4 isolate (1.1 %, 1/90) had strong biofilm-forming ability and 13 isolates (14.4 %, 13/90) had weak biofilm-forming ability. Genomic analysis revealed that Cronobacter spp. have a relatively stable core-genome and an increasing pan-genome size. Plasmid IncFIB (pCTU3) was prevalent in this genus and some contained 14 antibacterial biocide- and metal-resistance genes (BMRGs) including copper, silver, and arsenic resistant genes. Plasmid IncN_1 was predicted to contain 6 ARGs. This is the first time that a multi-drug resistance IncN_1 type plasmid has been reported in Cronobacter spp. Genomic variations with respect to BMRGs, virulence genes, antimicrobial resistance genes (ARGs), and genes involved in biofilm formation were observed among strains of this genus. There were apparent differences in copies of bcsG and flgJ between the biofilm-forming group and non-biofilm-forming group, indicating that these two genes play key roles in biofilm formation. The findings of this study have improved our understanding of the contamination characteristics and genetic basis of Cronobacter spp. in PIF and FUF and their production environment in China and provide important guidance to reduce contamination with this pathogen during the production of PIF and FUF.

Synthesis of a Metalla[2]catenane, Metallarectangles and Polynuclear Assemblies from Di(N-Heterocyclic Carbene) Ligands.

The 2,7-fluorenone-linked bis(6-imidazo[1,5-a]pyridinium) salt H2-1(PF6)2 reacts with Ag2O in CH3CN to yield the [2]catenane [Ag4(1)4](PF6)4. The [2]catenane rearranges in DMF to yield two metallamacrocycles [Ag2(1)2](PF6)2. 2,7-Fluorenone-bridged bis-(imidazolium) salt H2-L(PF6)2 (L = 2a, 2b) react with Ag2O in CH3CN to yield metallamacrocycles [Ag2(L)2](PF6)2 with interplanar distances between the fluorenone rings too small for [2]catenane formation. Intra- and intermolecular p···p interactions between the fluorenone groups were observed by X-ray crystallography. The strongly kinked 2,7-fluorenone bridged bis(5-imidazo[1,5-a]pyridinium) salt H2-4(PF6)2 reacts with Ag2O to yield [Ag2(4)(CN)](PF6) while the tetranuclear assembly [Ag4(4)2(CO3)](PF6)2 was obtained in the presence of K2CO3.

Influence of health education based on the transtheoretical model on kinesiophobia levels and rehabilitation outcomes in elderly patients undergoing total knee arthroplasty.

Objective: In this study, we evaluated the effectiveness of health education based on the transtheoretical model in reducing symptoms of kinesiophobia and enhancing rehabilitation outcomes among elderly patients post-total knee arthroplasty. Methods: Elderly patients post-knee replacement surgery were randomly divided into a control group, which received standard health education, and an experimental group, which received transtheoretical model-based health education. The intervention commenced on the day after surgery and continued for a duration of six months. Assessments of kinesiophobia scores, rehabilitation self-efficacy, and knee function were conducted before the intervention, and then at one, three, and six months postoperatively. Results: Between January 2022 and December 2022, 130 elderly patients who met the eligibility criteria were enrolled and subsequently randomly assigned into two groups of equal size. Comparable baseline characteristics were observed between the two groups The experimental group demonstrated lower kinesiophobia scores and higher scores in rehabilitation self-efficacy and knee function at one, three, and six months following surgery, compared to the control group. Conclusion: Health education based on a transtheoretical model reduces the symptoms of kinesiophobia and enhances rehabilitation self-efficacy and knee functions in elderly patients after knee replacement surgery.

Recurrent Cerebral Venous Sinus Thrombosis Occurred in an Acute Lymphoblastic Leukemia Child with Mutated Lipoprotein Lipase Gene during Asparaginase Therapy.

Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Uterine tumors resembling ovarian sex cord tumors: A retrospective analysis of 7 cases from a single institution.

To investigate the clinicopathological features, diagnosis, surgical treatment and prognosis of uterine tumors similar to ovarian sex cord tumors (UTROSCT). The clinical data, surgical approach, histopathological, and immunohistochemical features of 7 cases of UTROSCTs were retrospectively reviewed and followed up. All 4 patients were premenopausal women. The most common clinical presentation was menorrhagia (n = 4) followed by postmenopausal lower abdominal mass (n = 2) and postmenopausal bleeding (n = 1). Gynecological ultrasonography suggested uterine fibroids in 4 cases, adenomyosis with uterine fibroids in 2 cases, and an intrauterine mass in 1 case. Pelvic MRI was performed preoperatively in only 2 cases, and both indicated uterine fibroid degeneration, including 1 patient with suspected malignancy. Preoperative serum tumor markers were measured in 6 patients, and only 1 patient had elevated CA125 levels, up to 158 U/mL. Total hysterectomy with bilateral adnexectomy or salpingectomy was the most common treatment pattern (n = 6). The tumors were located within the myometrium (n = 4), submucosa (n = 1), and isthmus to external cervical os (n = 1), with a range of 2 to 12 (mean = 8) cm. Edema and degeneration were observed in 2 cases, and necrosis in 1 case. Postoperative follow-up ranged from 31 to 82 (mean = 43) months. Unfortunately, 1 patient died at 54 months of follow-up without undergoing hysterectomy. The remaining 6 cases showed no tumor recurrence or metastasis after surgery. Histological examination revealed a tumor composed of epithelioid tumor-like cells arranged in cords, trabeculae, and nests. All 7 tumors showed expression of 2 sex cord differentiation markers. Furthermore, all tumors expressed the smooth muscle marker, while epithelial marker CK (4/7). endometrial stromal marker CD10(0/7). The Ki-67 proliferation index was found to be <5% (5/7). The option of total hysterectomy may be considered for women who do not have any fertility requirements. However, for young women who desire to maintain their reproductive capacity, surgery to preserve the uterus may be an alternative, although it necessitates careful postoperative monitoring. In terms of follow-up monitoring, MRI is more suitable than ultrasound. The diagnosis of UTROSCT heavily relies on histopathological examination and immunohistochemical analysis.

HLA-B*35:01-mediated activation of emodin-specific T cells contributes to Polygonum multiflorum thunb. -induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: HLA-B*35:01 has been identified as a risk allele for Polygonum multiflorum Thunb.-induced liver injury (PMLI). However, the immune mechanism underlying HLA-B*35:01-mediated PMLI remains unknown. AIM OF THE STUDY: To characterize the immune mechanism of HLA-B*35:01-mediated PMLI. MATERIALS AND METHODS: Components of P. multiflorum (PM) bound to the HLA-B*35:01 molecule was screened by immunoaffinity chromatography. Both wild-type mice and HLA-B*35:01 transgenic (TG) mice were treated with emodin. The levels of transaminases, histological changes and T-cell response were assessed. Splenocytes from emodin-treated mice were isolated and cultured in vitro. Phenotypes and functions of T cells were characterized upon drug restimulation using flow cytometry or ELISA. Emodin-pulsed antigen-presenting cells (APCs) or glutaraldehyde-fixed APCs were co-cultured with splenocytes from emodin-treated transgenic mice to detect their effect on T-cell activation. RESULTS: Emodin, the main component of PM, could non-covalently bind to the HLA-B*35:01-peptide complexes. TG mice were more sensitive to emodin-induced immune hepatic injury, as manifested by elevated aminotransferase levels, infiltration of inflammatory cells, increased percentage of CD8+T cells and release of effector molecules in the liver. However, these effects were not observed in wild-type mice. An increase in percentage of T cells and the levels of interferon-γ, granzyme B, and perforin was detected in emodin-restimulated splenocytes from TG mice. Anti-HLA-I antibodies inhibited the secretion of these effector molecules induced by emodin. Mechanistically, emodin-pulsed APCs failed to stimulate T cells, while fixed APCs in the presence of emodin could elicit the secretion of T cell effector molecules. CONCLUSION: The HLA-B*35:01-mediated CD8+ T cell reaction to emodin through the P-I mechanism may contribute to P. multiflorum-induced liver injury.