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Abstract N. neocaledoniensis is a very rare infectious pathogen that causes human disease, particularly in immunocompromised individuals. In this case report, we describe the successful diagnosis of N. neocaledoniensis in a patient confirmed by mNGS and the treatment of multiple skin abscesses due to N. neocaledoniensis infection. mNGS is an important diagnostic method complementary to routine bacterial culture and identification methods, especially for rare, novel, co-infected pathogens, and pathogens that are difficult to culture. This report may provide a reference for the clinical treatment and diagnosis of N. neocaledoniensis infection in humans.

Fixation is a necessary tea processing step that affects the quality of tea, including its aroma. However, there are no guidelines to follow whether the Cyclocarya paliurus leaves need to be fixated to produce tea. The aim of this study was to determine the volatile metabolites in fixated and unfixated C. paliuru s tea by gas chromatography-mass spectrometry in order to identify the volatile compounds that differentiate them and establish the key aroma compounds. Compared with the unfixated tea, the fixated tea had higher contents of amines, phenols, nitrogen compounds, ether, alcohol, terpenoids, ester and aromatics. A total of 147 metabolites that differentiated both types of teas were identified using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Among them, 22 and 25 volatile compounds of teas processed without and with fixation, respectively, had relative odor activity values greater than 1. These metabolites had green, fruity, sweet, woody, herbal, floral, fresh, spicy, earthy and waxy odor. This study showed that fixation technology improved the quality of C. paliurus tea, which provided the basis for the production of C. paliurus tea, and promoted the standardization of the preparation technology of C. paliurus tea.

An individual’s social adaptation is affected by their early maladaptive schemas. Previous studies have shown that early maladaptive schemas may be intergenerationally transmitted in families. It is important to explore the intergenerational effect of early maladaptive schemas on adolescents’ social adaptation, as they are in a critical period of growth and development. In this study, a cross-sectional design and questionnaire survey were used to collect data to explore the intergenerational influence of early maladaptive schemas in families and their relationship with adolescents’ social adaptation. The participants were 201 adolescents aged 12 to 16 years and their primary caregivers (father or mother), of whom 125 (62.2%) were boys and 76 (37.8%) were girls. There were 70 fathers (34.8%) and 131 mothers (65.2%). Chinese adolescents and their primary caregivers were surveyed using paired questionnaires, and the Young Schema Questionnaire (short form) and Adolescent Social Adaptation Scale were completed. The results show that adolescents’ early maladaptive schema plays an intermediary role between parents’ early maladaptive schema and adolescents’ social adaptation. Parental mistrust/abuse and insufficient self-control schemas affected adolescents’ social adaptation through the mediating effect of their corresponding schemas. Our results reveal the negative impact path of parents’ early maladaptive schemas on adolescents’ social adaptation and provide a new direction for the clinical practice of adolescent family therapy.

Abstract This study aimed to improve the comprehensive utilization value of rice bran by investigating catalysts for the methyl esterification reaction of rice bran oil deodorized distillates and preparing phytosterol nanoparticles for addition to yogurt. Fe2(SO4)3 was found to be an effective catalyst, achieving a methyl esterification rate of 98.07 ± 0.23% under optimal conditions. Then, phytosterol nanoparticles were prepared and added to yogurt, resulting in stable addition with the pH decreased from 4.23 ± 0.01 to 4.02 ± 0.01 and the titratable acidity increased from 106.48 ± 0.85 °T to 117.07 ± 0.82 °T during storage. The addition of phytosterol nanoparticles increased the apparent viscosity from 0.68 ± 0.01 Pa s to 0.72 ± 0.02 Pa s and the G* from 80.01 ± 5.50 Pa to 91.80 ± 1.99 Pa, resulting in thicker and more elastic texture. Phytosterol nanoparticle improves the dispersion and stability of phytosterols in yogurt, thus making it stable to be added to yogurt. Fe2(SO4)3 is a suitable catalyst for the methyl esterification reaction of rice bran oil deodorized distillates, and the addition of rice bran phytosterol nanoparticles to yogurt can enhance its texture and nutritional value, offering a promising strategy for producing high value‐added products from rice bran.

Abstract Family is an important system that influences children’s social adjustment. Parents are an important member of the family system, and their parental child-rearing gender-role attitudes (PCGA) will have a significant impact on their children’s social adjustment. This study used a sampling method to compare the intergenerational differences between family members’ PCGA, identity with parents and social adjustment in single- and two-parent families through 931 single-parent families and 3732 two-parent families in Suzhou, China. The study explored the mediating role of children’s identity with parents on parents’ PCGA and children’s social adjustment in different family structures. The results showed that: (1) parents’ masculinity rearing, femininity rearing of PCGA and children’s social adjustment in two-parent families were significantly higher than those in single-parent families; (2) children’s identity with parents mediated the relationship between femininity rearing of parents’ PCGA and children’s social adjustment; (3) the mediated model of children’s identity with parents was found to be significantly different between single-parent and two-parent families.

Heavy metal(loid) (HM) contamination is a significant threat to wetland ecosystem. However, contamination risks of HMs in overlying water of small wetlands, which are easily ignored because of their minor occupancy in an overall area, are nearly unknown. A total of 36 water samples containing six HMs were collected from the urban and rural small wetlands of Urumqi in China, and the contamination levels and probabilistic health risks caused by HMs were assessed using the Nemerow pollution index (NPI) and the health risk assessment model introduced by the US EPA. The results revealed that the average concentration of Hg in the urban and rural small wetlands surpassed the Class II thresholds of the Environmental Quality Standards for Surface Water (GB 3838-2002) by factors of 3.2 and 5.0 times, respectively. The overall contamination levels of HMs in the small wetlands fall into the high contamination level. Results of a health risk assessment indicated that non-carcinogenic health risk of the investigated HMs are found to be lower than the acceptable range for adults, but higher than the acceptable range for children. Meanwhile, As falls into the low carcinogenic risk level, whereas Cd falls into the very low carcinogenic risk level. Overall, HMs in rural small wetlands showed relatively higher contamination levels and probabilistic health risks than that of urban small wetlands. In addition, As was identified as the dominant health risk factor in the overlying water of small wetlands in the study area. Findings of this study provide scientific support needed for the prevention of HM contamination of small wetlands in arid zones.

The increasing public demand for fresh products has catalyzed the requirement for cold chain logistics distribution systems. However, challenges such as temperature control and delivery delays have led a significant product loss and increased costs. To improve the current situation, a novel approach to optimize cold chain logistics distribution for fresh products will be presented in the paper, utilizing a hybrid Tabu-Grey wolf optimizer (TGWO) algorithm. The proposed hybrid approach combines Tabu search (TS) and Grey wolf optimizer (GWO), employing TS for exploration and GWO for exploitation, aiming to minimize distribution costs in total and establish efficient vehicle scheduling schemes considering various constraints. The effectiveness of the TGWO algorithm is demonstrated through experiments and case studies compared to other heuristic algorithms. Comparative analysis against traditional optimization methods, including Particle swarm optimization (PSO), Whale optimization algorithm (WOA), and original GWO, highlights its superior efficiency and solution quality. This study contributes theories by demonstrating the efficacy of hybrid optimization techniques in complex supply chain networks and dynamic market environments. The practical implication lies in the implementation of TGWO to bolster distribution efficiency, cost reduction, and product quality maintenance throughout the logistics process, offering valuable insights for operational and strategic improvements by decision-makers. However, the study has limitations in generalizability and assumptions, suggesting future research areas including exploring new search operators, applying additional parameters, and using the algorithm in diverse real-life scenarios to improve its effectiveness and applicability.

Potentially toxic elements (PTEs) pose a significant threat to the groundwater system and human health. Pollution and the potential risks of PTEs in groundwater in the Kǒnqi River Basin (KRB) of the northwest arid zones of China are still unknown. A total of 53 groundwater samples containing eight PTEs (Al, As, Cd, Cu, Mn, Pb, Se, and Zn) were collected from the KRB, and the pollution levels and probabilistic health risks caused by PTEs were assessed based on the Nemerow Index (NI) method and the health risk assessment model. The results revealed that the mean contents of Al, As, and Mn in the groundwater surpassed the Class III threshold of the Standard for Groundwater Quality of China. The overall pollution levels of the investigated PTEs in the groundwater fall into the moderate pollution level. The spatial distributions of contents and pollution levels of different PTEs in the groundwater were different. Health risk assessment indicated that all the investigated PTEs in groundwater in the KRB may pose a probabilistic non-carcinogenic health risk for both adults and children. Moreover, As may pose a non-carcinogenic health risk, whereas the non-carcinogenic health risk posed by the other seven PTEs in groundwater will not have the non-carcinogenic risks. Furthermore, As falls into the low carcinogenic risk level, whereas Cd falls into the very low carcinogenic risk level. Overall, As was confirmed as the dominant pollution factor and health risk factor of groundwater in the KRB. Results of this study provide the scientific basis needed for the prevention and control of PTE pollution in groundwater.

This study aimed to investigate the efficacy of supercritical CO2 (SC-CO2) extraction in enhancing the extraction rate, purity, and antioxidant activity of Indocalamus latifolius (Keng) McClure (Poaceae) leaf terpenoids (ILLTs). Crude extracts obtained from leaves were subjected to qualitative and quantitative analyses, revealing neophytadiene, phytol, β-sitosterol, β-amyrone, squalene, and friedelin as the primary terpenoid constituents, identified through gas chromatography–mass spectrometry (GC-MS). Compared with steam distillation extraction (SD), simultaneous distillation extraction (SDE), ultra-high pressure-assisted n-hexane extraction (UHPE-Hex), ultra-high pressure-assisted ethanol extraction (UHPE-EtOH), ultrasound-assisted n-hexane extraction (UE-Hex), and ultrasound-assisted ethanol extraction (UE-EtOH), SC-CO2 exhibited a superior ILLT extraction rate, purity, and antioxidant activity. Scanning electron microscopy (SEM) observations of the residues further revealed more severe damage to both the residues and their cell walls after SC-CO2 extraction. Under optimal parameters (4.5 h, 26 MPa, 39 °C, and 20% ethyl alcohol), the ILLT extraction rate with SC-CO2 reached 1.44 ± 0.12 mg/g, which was significantly higher than the rates obtained by the other six methods. The subsequent separation and purification using WelFlash C18-l, BUCHI-C18, and Sephadex LH-20 led to an increase in the purity of the six terpenoid components from 12.91% to 93.34%. Furthermore, the ILLTs demonstrated cytotoxicity against HepG2 cells with an IC50 value of 148.93 ± 9.93 μg/mL. Additionally, with increasing concentrations, the ILLTs exhibited an enhanced cellular antioxidant status, as evidenced by reductions in both reactive oxygen species (ROS) and malondialdehyde (MDA) levels.

In the study, natural deep eutectic solvents (NADESs) were used as alternatives to traditional chemical solvents for the extraction of polyphenols from Elaeagnus angustifolia L. Nine NADESs were tested for the first time and compared with ethanol and water (traditional solvents) regarding the extraction of phenolic compounds from E. angustifolia L. These solvents were particularly effective at extracting polyphenols, whose low water solubility usually requires high amounts of organic solvents. The solvent based on choline chloride and malonic acid provided optimal results and was selected for further optimization. The effects of material-to-liquid ratio, ultrasound time, and ultrasound temperature on the extraction efficiency were studied through single-factor experiments. These parameters were optimized by Box–Behnken design using response surface methodology. The optimal conditions identified were 49.86 g/mL of material-to-liquid ratio, 31.10 min of ultrasound time, and 62.35 °C of ultrasound temperature, resulting in a high yield of 140.30 ± 0.19 mg/g. The results indicated that the NADES extraction technique provided a higher yield than the conventional extraction process. The antioxidant activity of the extract of polyphenols from E. angustifolia L. was determined, and UPLC–IMS–QTOF–MS was used to analyze the phenolic compounds in it. The results revealed that the scavenging ability of 1,1-diphenyl-2-picryl-hydrazil and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) extracted by NADES was higher than that of polyphenols extracted by water and ethanol. Furthermore, a total of 24 phenolic compounds were identified in the extract. To the best of our knowledge, this is the first study in which a green and efficient NADES extraction method has been used to extract bioactive polyphenols from E. angustifolia L., which could provide potential value in pharmaceuticals, cosmetics, and food additives.

Citrinin (CIT), a secondary metabolite produced by the filamentous fungi Monascus species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of Monascus-derived products. CIT synthesis is mediated through the pksCT gene and modified by multiple genetic factors. Here, the regulatory effects of two pksCT transcripts, pksCTα, and pksCTβ, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically mrl3, mrl5, mrr1, and mrr5 in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing pksCT has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in Monascus, thus providing a foundation for future research.

In order to study the effect of both greenhouse and forest cultivating environments on Stropharia rugosoannulata, its volatile aroma compounds were measured by a headspace solid phase micro extractions—gas chromatograph—mass spectrometer (SPME–GC–MS). The optimal adsorption temperature was 75 °C and the optimal adsorption time was 40 min. A total of 36 volatile aroma compounds were identified by GC–MS, including 8 aldehydes, 2 ketones, 4 alcohols, 15 alkenes, and 4 alkanes. Hexanal, 3-Octanone, 2-Undecanone, (E)-Nerolidol, and (Z)-β-Farnesene made great aromatic contributions. Among them, Hexanal, 3-Octanone, 2-Undecanone were the key aroma compounds for which odor activity values (OAVs) were more than 1. (E)-Nerolidol showed odor modification in the forest samples and showed a key aroma effect in greenhouse samples. (Z)-β-Farnesene showed odor modification in greenhouse samples. 3-Octanone was the largest contributing compound for which the OAV was more than 60. The total content of volatile aroma compounds first increased and then decreased with growth time; it reached the highest level at 48 h: 2203.7 ± 115.2 μg/kg for the forest environment and 4516.6 ± 228.5 μg/kg for the greenhouse environment. The aroma was the most abundant at this time. All samples opened their umbrella at 84 h and become inedible. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS–DA) were combined to analyze the aroma difference of S. rugosoannulata under two cultivation modes. PCA and HCA could effectively distinguish the aroma difference in different growth stages. Under different culturing methods, the aroma substances and their changes were different. The samples were divided into two groups for forest cultivation, while the samples were divided into three groups for greenhouse cultivation. At the end of growth, the aroma of S. rugosoannulata with the two cultivation modes was very similar. OPLS–DA clearly distinguished the differences between the two cultivation methods; 17 key aroma difference factors with variable importance projection (VIP) > 1 were obtained from SPLS–DA analysis.

Objective: Studies about the epidemiology and risk factors of late onset of sepsis (LOS) in preterm very low birth weight (PVLBW) infants of developing countries are limited and variable. The objective of this study was to explore the epidemiology, risk factors and pathogens of LOS in VLBW infants in a Chinese tertiary hospital. Methods: Data concerning demographies, pathogens, risk factors and outcomes of LOS were collected in a cohort of 710 VLBW infants discharged from January 2012 to December 2018. Chi-square, t-test and multivariable logistic regression analysis were used to identify risk factors. Results: The overall incidence of LOS was 24.08% and blood culture-proven sepsis was 19.58%. Gram-negative bacteria accounted for 57.93%, and 32.41% of the isolates were Klebsiella pneumoniae. LOS led to a longer hospital stay, higher hospitalization cost and higher mortality compared to infants without LOS. Mortality in Gram-negative or fungi LOS was higher than in Gram-positive LOS. The factor of PVLBW infants with registered permanent residence (PR) was associated with 80% lower likelihood of LOS compared to those without registered PR (P = 0.000, 95% CI 0.096–0.420). Infants with thrombocytopenia had 2.5 times LOS of control (P = 0.014, CI 1.210–5.132). Duration of parenteral nutrition was a risk of LOS (P = 0.009, CI 1.010–1.069). Conclusion: Gram-negative bacteria, especially Klebsiella pneumonia, were the dominant pathogens in this study. Social factors might be a risk of LOS in PVLBW infants in developing countries. Taking measures to reduce the duration of parenteral nutrition may be helpful in decreasing the incidence of LOS. Awareness of thrombocytopenia may help to recognized diagnosis of LOS.

Flavonoids are major active small-molecule compounds in bamboo leaves, which can be easily obtained from the bamboo leaves extraction residues (BLER) after the polysaccharides extraction. Six macroporous resins with different properties were screened to prepare and enrich isoorientin (IOR), orientin (OR), vitexin (VI), and isovitexin (IVI) from BLER, and the XAD-7HP resin with the best adsorption and desorption performance was selected for further evaluation. Based on the static adsorption experiments, the experimental results showed that the adsorption isotherm fitted well with the Langmuir isotherm model, and the adsorption process was better explained by the pseudo-second-order kinetic model. After the dynamic trial of resin column chromatography, 20 bed volume (BV) of upload sample and 60% ethanol as eluting solvent was used in a lab scale-up separation, and the results demonstrated that the content of four flavonoids could be increased by 4.5-fold, with recoveries between 72.86 and 88.21%. In addition, chlorogenic acid (CA) with purity of 95.1% was obtained in water-eluted parts during dynamic resin separation and further purified by high-speed countercurrent chromatography (HSCCC). In conclusion, this rapid and efficient method can provide a reference to utilize BLER to produce high-value-added food and pharmaceutical products.

Monascus red pigments (MRPs) are mainly used as natural food colorants; however, their application is limited due to their poor stability. To expand their areas of application, we investigated the binding constants and capacity of MRPs to whey protein isolate (WPI) and whey protein hydrolysate (WPH) and calculated the surface hydrophobicities of WPI and WPH. MRPs were combined with WPI and WPH at a hydrolysis degree (DH) of 0.5% to form the complexes (DH = 0.0%) and (DH = 0.5%), respectively. Subsequently, the structural characteristics of complex (DH = 0.5%) and WPI were characterized and the color retention rates of both complexes and MRPs were investigated under different pretreatment conditions. The results showed that the maximum binding constant of WPI with MRPs was 0.670 ± 0.06 U−1 and the maximum binding capacity was 180 U/g. Furthermore, the thermal degradation of complex (DH = 0.0%), complex (DH = 0.5%), and MRPs in a water bath at 50–100 °C followed a first-order kinetic model. Thus, the interaction of WPI with MRPs could alter the protein conformation of WPI and effectively protect the stability of MRPs.

Monascus red pigments (MRPs), which are a kind of natural colorant produced by Monascus spp., are widely used in the food and health supplements industry but are not very stable during processing and storage. Thus, MRPs were embedded into liposome membranes using a thin-film ultrasonic method to improve stability in this study. Monascus red pigments liposomes (MRPL) exhibited spherical unilamellar vesicles (UV) with particle size, polydispersity indexes (PDI), and zeta potential of 20–200 nm, 0.362 ± 0.023, and −42.37 ± 0.21 mV, respectively. pH, thermal, light, metal ion, storage, and in vitro simulated gastrointestinal digestion stability revealed that, compared with free MRPs, liposomes embedding significantly enhanced the stability of MRPs when exposed to adverse environmental conditions. Furthermore, anticancer assay suggested that MRPL exhibited a stronger inhibitory effect on MKN-28 cells by damaging the integrity of cells, with the IC50 value at 0.57 mg/mL. Overall, MRPLs possess stronger stability in external environment and in vitro simulated digestion with greater anticancer activity, indicating that MRPLs have the potential for promising application in the functional foods and pharmaceutical industries.

Zhejiang Ophiopogonjaponicus (ZOJ) is a specific variety of Ophiopogon japonicus with characteristic steroidal saponins and homoisoflavonoids, which are also main pharmacodynamic constituents with clinical effects, including curing inflammation and cardiovascular diseases. However, few analysis methods were applied to simultaneously and quantitatively determine two kinds of its constituents, and hazardous organic solvents are mostly used for extraction. In this study, a new validated simultaneous extraction and determination method for four characteristic steroidal saponins and homoisoflavonoids in ZOJ was established by ionic liquid–ultrasonic extraction (IL-UAE) combined with HPLC-DAD-ELSD analysis, which can be used for the quality control of ZOJ. Chromatographic separation was performed with a DAD wavelength at 296 nm, and the ELSD parameters of the drift tube temperature (DTT), atomizer temperature (AT), and nitrogen gas pressure (NGP) were set at 20% heating power, 70 °C, and 25 psi, respectively. The optimal IL-UAE conditions were 1 mol/L [Bmim]CF3SO3 aqueous solution, a liquid–material ratio of 40 mL/g, and an ultrasonic time of 60 min. The proposed method is reliable, reproducible, and accurate, which were verified with real sample assays. Consequently, this work will be helpful for the quality control of ZOJ. It can also present a promising reference for the simultaneous extraction and determination of different kinds of constituents in other medicinal plants.

Silicone rubber insulators (SRIs) are widely used in high-voltage power grids. Due to high-voltage fields and harsh environmental conditions, SRIs eventually deteriorate with use in the power grid, decreasing their insulating performance and operational life and contributing to transmission line failures. Therefore, quantitatively assessing the aging status of SRIs is crucial. In this study, we evaluated the viability of the magnetic resonance method for assessing the age of SRIs at the level of chemical structure; we built and made a portable magnetic resonance sensor, and evaluated the sensor’s functionality. By measuring the SRI sheds at various service times, it was discovered that the equivalent transverse relaxation time, T2eff, can describe the degree of aging of the SRIs. The results of the magnetic resonance measurements were also compared with those of the static contact angle method, and the two measurement methods yielded the same conclusions. However, the magnetic resonance method was more sensitive than the one using the static contact angle method.

Mounting studies demonstrated both chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection might be associated not only with an increased risk of hepatocellular carcinoma but also extrahepatic malignancies, i.e., gastric cancer (GC). However, a quantitative result addressing the association between HBV/HCV infection and GC development is scarce. A systematic search to identify the eligible studies was performed in four databases, including MEDLINE, EMBASE, Cochrane Library, and the PsychINFO. The relationship between HBV/HCV infection and the risk of GC was quantified by calculating the hazard ratio (HR) with a 95% confidence interval (CI). More methodologies of this study were available in the PROSPERO (ID: CRD42021243719). Thirteen included studies involving 7,027,546 individuals (mean age, 42.6-71.9 years) were enrolled in the pooled analyses. Two articles provided the clinical data of both HBV and HCV infections. The proportion of high methodological quality studies was 76.9% (10/13). Synthetic results from 10 eligible studies of HBV showed that HBV infection was associated with a significantly higher risk of GC when compared with the healthy controls without HBV infection (pooled HR, 1.26; 95% CI, 1.08–1.47; P = 0.003; heterogeneity, I2 = 89.3%; P< 0.001). In line with this finding, the combined effect derived from five included studies of HCV also supported a significant positive association between chronic HBV infection and GC development (pooled HR, 1.88; 95% CI, 1.28–2.76; P = 0.001; heterogeneity, I2 = 74.7%; P = 0.003). In conclusion, both chronic HBV and HCV infections were related to a high risk of GC. The plausible mechanisms underlying such association might be correlated to HBV/HCV infection-induced persistent inflammation, immune dysfunction, and cirrhosis.Systematic Review RegistrationPROSPERO (http://www.crd.york.ac.uk/PROSPERO), identifier (CRD42021243719).

During pregnancy, the maternal immune system undergoes major adaptive modifications that are necessary for the acceptance and protection of the fetus. It has been postulated that these modifications are temporary and limited to the time of pregnancy. Growing evidence suggests that pregnancy has a long-term impact on maternal health, especially among women with pregnancy complications, such as preeclampsia (PE). In addition, the presence of multiple immunological-associated changes in women that remain long after delivery has been reported. To explain these long-term modifications, we hypothesized that pregnancy induces long-term immunological memory with effects on maternal well-being. To test this hypothesis, we evaluated the immunological phenotype of circulating immune cells in women at least 1 year after a normal pregnancy and after pregnancy complicated by PE. Using multiparameter flow cytometry (FCM) and whole-genome bisulfite sequencing (WGBS), we demonstrate that pregnancy has a long-term effect on the maternal immune cell populations and that this effect differs between normal pregnancy and pregnancy complicated by PE; furthermore, these modifications are due to changes in the maternal methylation status of genes that are associated with T cell and NK cell differentiation and function. We propose the existence of an “immunological memory of pregnancy (IMOP)” as an evolutionary advantage for the success of future pregnancies and the proper adaptation to the microchimeric status established during pregnancy. Our findings demonstrate that the type of immune cell populations modified during pregnancy may have an impact on subsequent pregnancy and future maternal health.

BackgroundRecent research of clear cell renal cell carcinoma (ccRCC) is focused on the tumor immune microenvironment (TIME). Chromatin accessibility is critical for regulation of gene expression. However, its role in different immunological subtypes of ccRCC based on immune cell infiltration has not been systematically studied.MethodsFive hundred thirty patient data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) were adopted to estimate immune cell infiltration. Twenty-four types of immune cells were evaluated with single-sample Gene Set Enrichment Analysis (ssGSEA). Patients were divided into two clusters based on immune cell infiltration. Systematic chromatin accessibility analysis was conducted based on the two clusters.ResultsWe compared the relative expression of the immune gene signatures among 530 patients of TCGA-KIRC using ssGSEA. Overall survival (OS) analysis revealed 10 types of immune cells were significantly associated with prognosis. Patients were divided into two clusters based on 24 types of immune cell infiltration. Immune cell signals as well as PD-1/PD-L1 signal were higher in cluster 1. Among the two clusters, 2,400 differential peaks were found in TCGA-KIRC Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) data. The distribution of differential peaks and prognosis-related immune cells in 23 chromosomes are essentially the same. There is no peak distribution downstream. The proportion of peaks upstream of the 5’ transcription start site decreases, and both sides of binding regions of the TSS 0.1-1 kb becomes smaller. Enrichment analysis of GO and KEGG of these differential peaks showed that they are remarkably related to the immune regulation in tumor microenvironment. Known motifs and de novo motifs were found by linking motif annotations to different peaks. Survival analysis of related motif transcription factors were prognostic. The GSEA enrichment analysis showed that high SP1 expression positively correlates with TGF-beta signaling and inflammatory response, while negatively correlates with TNF-alpha signaling via NFKB. High KLF12 expression negatively correlates with interferon gamma response, IL2-STAT5 signaling, TNF-alpha signaling via NFKB, IL6-JAK-STAT3 signaling.ConclusionThe abnormality of chromatin accessibility may play an important regulatory role in ccRCC immunity.

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID‐19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.

Purpose: Accumulative studies suggest the Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) to be potential biomarkers; however, their prognostic value remains debatable. Our meta-analysis focused on assessing the accurate prognostic value of GPS and mGPS in patients with renal cell carcinoma (RCC) in addition to their effectiveness.Methods: To investigate the relationship between mGPS/GPS and prognostic value in patients with RCC, we performed a comprehensive retrieval of relevant articles from databases such as PubMed, Embase, Web of Science, and Medline up to February 1, 2020. STATA 15.0 software was used to obtain pooled hazard ratios (HRs) and their 95% confidence intervals for survival outcome, including overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). A formal meta-analysis of these outcomes was performed.Results: In total, 2,691 patients with RCC were enrolled from 15 cohort studies. Higher GPS/mGPS (GPS/mGPS of 2) indicated poorer OS, CSS, PFS, and RFS in patients with RCC. Similarly, medium GPS/mGPS (GPS/mGPS of 1) also had a significant association with poorer OS, CSS, PFS, and RFS but superior than higher GPS/mGPS in these patients.Conclusion: GPS and mGPS are effective biomarkers for predicting prognosis in patients with RCC, and higher GPS and mGPS are closely related to inferior survival outcomes. More randomized controlled trials are needed to investigate the promising value of GPS/mGPS in the future.

Objective. To develop a quantitative analysis of multicomponents by single-marker (QAMS) method for the simultaneous determination of polar active components in Fructus Corni. Methods. Loganin was selected as the internal reference, and the relative correction factors (RCFs) of gallic acid, 5-hydroxymethyl-2-furfural, morroniside, sweroside, cornin, 7α-O-methylmorroniside, 7β-O-methylmorroniside, 7α-O-ethylmorroniside, 7β-O-ethylmorroniside, and cornuside were established. The contents of multicomponents were then calculated based on their RCFs, respectively. Contents of the 11 components were also calculated by external standard method and compared with those of the QAMS method. Results. The contents of the 11 components in 21 crude and 10 processed Fructus Corni products were measured. No significant difference was found in the quantitative results of the QAMS and external standard methods. Conclusion. QAMS could serve as an accurate and convenient method in determining the polar and active components in Fructus Corni and its processed products.

Ionic liquids (ILs), known as environmentally benign “green” solvents, were developed as an optimal solvent for the green extraction and separation field. In this paper, an ionic liquid-based ultrasonic-assisted extraction (IL-UAE) of flavonoids (FVs) from bamboo leaves of Phyllostachys heterocycla was developed for the first time. First, 1-butyl-3-methylimidazolium bromide ([Bmim] Br), with the best extraction efficiency, was selected from fifteen ionic liquids with diverse structure, like carbon chains or anions. Then, the influencing parameters of ionic liquid (IL) concentration, liquid-solid ratio, ultrasonic time, and ultrasonic power, were investigated by single factor tests, and further optimized using response surface methodology (RSM). In the optimization experiment, the best conditions were 1.5 mol/L [BMIM]Br aqueous solution, liquid-solid ratio 41 mL/g, ultrasonic time 90 min, and ultrasonic power 300 W. Furthermore, the microstructures of bamboo leaves and the recovery of FVs and [BMIM]Br were also studied. Therefore, this simple, green and effective IL-UAE method has potentiality for the extraction of FVs from bamboo leaves for the large-scale operations.