Photocatalytic PAN Nanofibrous Membrane through Anchoring a Nanoflower-Branched CoAl-LDH@PANI Heterojunction for Organic Hazards Degradation and Oil-Containing Emulsified Wastewater Separation.

The synergistic treatment of oily wastewater containing organic hazards and emulsified oils remains a big challenge for membrane separation technology. Herein, the photocatalytic membrane, which combined the physical barrier and catalytic oxidation-driven degradation functionality, was fabricated via anchoring a nanoflower-branched CoAl-LDH@PANI Z-scheme heterojunction onto a porous polyacrylonitrile mat and using tannic acid as an adhesive. The assembly of such a Z-scheme heterojunction offered the superior photocatalytic degradation performance of soluble dyes and tetracycline (up to 94.3%) to the membrane with the improved photocatalytic activity of 2.33 times compared with the CoAl-LDH@pPAN membrane. Quenching experiments suggested that the •O2- was the most reactive oxygen species in the catalytic reaction system of the composite membrane. The greatly enhanced photocatalytic activity was attributed to the effective inhibition of photogenerated hole-electron combination using PANI as a carrier, with charge transferring from LDH to PANI. The possible photocatalytic degradation mechanism was proposed based on VB-XPS, electron spin resonance spectroscopy, and DRS technologies, which was confirmed by density functional theory calculation. Meanwhile, benefiting from the superhydrophilic/oleophobic feature and low oil adhesion, the membrane exhibited high permeability for isooctane emulsion (3990.39 L·m-2·h-1), high structure stability, and satisfactory cycling performance. This work provided a strategy to develop superwetting and photocatalytic composite membranes for treating complex multicomponent pollutants in the chemical industry.

6PPD-quinone affects the photosynthetic carbon fixation in cyanobacteria by extracting photosynthetic electrons.

Photosynthetic carbon fixation by cyanobacteria plays a pivotal role in the global carbon cycle but is threatened by environmental pollutants. To date, the impact of quinones, with electron shuttling properties, on cyanobacterial photosynthesis is unknown. Here, we present the first study investigating the effects of an emerging quinone pollutant, i.e., 6PPD-Q (N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone), on the cyanobacterium Synechocystis sp. over a 400-generation exposure period. Synechocystis sp. exhibited distinct sequential phases, including hormesis, toxicity, and eventual recovery, throughout this exposure. Extensive evidence, including results of thylakoid membrane morphological and photosynthetic responses, carbon fixation rate, and key gene/protein analyses, strongly indicates that 6PPD-Q is a potent disruptor of photosynthesis. 6PPD-Q accepts photosynthetic electrons at the plastoquinone QB site in photosystem II (PSII) and the phylloquinone A1 site in PSI, leading to a sustained decrease in the carbon fixation of cyanobacteria after an ephemeral increase. This work revealed the specific mechanism by which 6PPD-Q interferes with photosynthetic carbon fixation in cyanobacteria, which is highly important for the global carbon cycle.

Extracellular domains of CARs reprogramme T cell metabolism without antigen stimulation.

Metabolism is an indispensable part of T cell proliferation, activation and exhaustion, yet the metabolism of chimeric antigen receptor (CAR)-T cells remains incompletely understood. CARs are composed of extracellular domains-often single-chain variable fragments (scFvs)-that determine ligand specificity and intracellular domains that trigger signalling following antigen binding. Here, we show that CARs differing only in the scFv variously reprogramme T cell metabolism. Even without exposure to antigens, some CARs increase proliferation and nutrient uptake in T cells. Using stable isotope tracers and mass spectrometry, we observed basal metabolic fluxes through glycolysis doubling and amino acid uptake overtaking anaplerosis in CAR-T cells harbouring a rituximab scFv, unlike other similar anti-CD20 scFvs. Disparate rituximab and 14G2a-based anti-GD2 CAR-T cells are similarly hypermetabolic and channel excess nutrients to nitrogen overflow metabolism. Modest overflow metabolism of CAR-T cells and metabolic compatibility between cancer cells and CAR-T cells are identified as features of efficacious CAR-T cell therapy.

[Study of GCN repeats of PHOX2B gene among individuals from southwest China and diagnosis of two patients with Congenital central hypoventilation syndrome].

OBJECTIVE: To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). METHODS: The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. RESULTS: Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN)7, (GCN)13, (GCN)14, (GCN)15 and (GCN)20. The frequency of the (GCN)20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN)7/(GCN)20, (GCN)13/(GCN)20, (GCN)14/(GCN)20, (GCN)15/(GCN)20, (GCN)20/(GCN)20. The homozygous genotypes were all (GCN)20/(GCN)20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN)20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the,Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN)20/(GCN)25 and (GCN)20/(GCN)30, respectively. CONCLUSION: It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

Predicting 1-, 3-, 5-, and 8-year all-cause mortality in a community-dwelling older adult cohort: relevance for predictive, preventive, and personalized medicine.

Background: Population aging is a global public health issue involving increased prevalence of age-related diseases, and concomitant burden on medical resources and the economy. Ninety-two diseases have been identified as age-related, accounting for 51.3% of the global adult disease burden. The economic cost per capita for older people over 60 years is 10 times that of the younger population. From the aspects of predictive, preventive, and personalized medicine (PPPM), developing a risk-prediction model can help identify individuals at high risk for all-cause mortality and provide an opportunity for targeted prevention through personalized intervention at an early stage. However, there is still a lack of predictive models to help community-dwelling older adults do well in healthcare. Objectives: This study aims to develop an accurate 1-, 3-, 5-, and 8-year all-cause mortality risk-prediction model by using clinical multidimensional variables, and investigate risk factors for 1-, 3-, 5-, and 8-year all-cause mortality in community-dwelling older adults to guide primary prevention. Methods: This is a two-center cohort study. Inclusion criteria: (1) community-dwelling adult, (2) resided in the districts of Chaonan or Haojiang for more than 6 months in the past 12 months, and (3) completed a health examination. Exclusion criteria: (1) age less than 60 years, (2) more than 30 incomplete variables, (3) no signed informed consent. The primary outcome of the study was all-cause mortality obtained from face-to-face interviews, telephone interviews, and the medical death database from 2012 to 2021. Finally, we enrolled 5085 community-dwelling adults, 60 years and older, who underwent routine health screening in the Chaonan and Haojiang districts, southern China, from 2012 to 2021. Of them, 3091 participants from Chaonan were recruited as the primary training and internal validation study cohort, while 1994 participants from Haojiang were recruited as the external validation cohort. A total of 95 clinical multidimensional variables, including demographics, lifestyle behaviors, symptoms, medical history, family history, physical examination, laboratory tests, and electrocardiogram (ECG) data were collected to identify candidate risk factors and characteristics. Risk factors were identified using least absolute shrinkage and selection operator (LASSO) models and multivariable Cox proportional hazards regression analysis. A nomogram predictive model for 1-, 3-, 5- and 8-year all-cause mortality was constructed. The accuracy and calibration of the nomogram prediction model were assessed using the concordance index (C-index), integrated Brier score (IBS), receiver operating characteristic (ROC), and calibration curves. The clinical validity of the model was assessed using decision curve analysis (DCA). Results: Nine independent risk factors for 1-, 3-, 5-, and 8-year all-cause mortality were identified, including increased age, male, alcohol status, higher daily liquor consumption, history of cancer, elevated fasting glucose, lower hemoglobin, higher heart rate, and the occurrence of heart block. The acquisition of risk factor criteria is low cost, easily obtained, convenient for clinical application, and provides new insights and targets for the development of personalized prevention and interventions for high-risk individuals. The areas under the curve (AUC) of the nomogram model were 0.767, 0.776, and 0.806, and the C-indexes were 0.765, 0.775, and 0.797, in the training, internal validation, and external validation sets, respectively. The IBS was less than 0.25, which indicates good calibration. Calibration and decision curves showed that the predicted probabilities were in good agreement with the actual probabilities and had good clinical predictive value for PPPM. Conclusion: The personalized risk prediction model can identify individuals at high risk of all-cause mortality, help offer primary care to prevent all-cause mortality, and provide personalized medical treatment for these high-risk individuals from the PPPM perspective. Strict control of daily liquor consumption, lowering fasting glucose, raising hemoglobin, controlling heart rate, and treatment of heart block could be beneficial for improving survival in elderly populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00342-4.

Design and assembly of Ag-decorated Bi2O3 @ 3D MXene Schottky heterojunction for the highly permeable and multiple-antifouling of fibrous membrane in the purification of complex emulsified oil pollutants.

Membrane separation technology has potential for purifying emulsified oily wastewater. However, the oils, soluble organic substances, and microorganisms can cause complex membrane fouling problems, thereby reducing the separation efficiency and service life. Herein, a highly permeable and multiple-antifouling composite membrane was prepared using porous PAN fibrous mat as support backbone for the assembly of Ag-decorated Bi2O3 @ 3D MXene Schottky heterojunction and hydrophilic TA as the adhesive. The unique arrangement of 3D MXene heterojunction and hydrophilic functionalization effectively broke through the limitation of separation flux and synergistically enhanced the anti-fouling performance of membrane. Such fibrous composite membrane achieved an exceedingly high permeability (2717-3328 L·m-2·h-1) for various emulsified oils, while ensuring excellent oil/water emulsion retention rate (99.59%) and good cycle stability. Meanwhile, the composite membrane displayed favorable photocatalytic degradation performance toward degrading MeB (96.1%) and antibacterial ability. Furthermore, the MD simulation and free radical trapping experiments were carried out to unravel the molecular interactions during the separation process and the photocatalytic mechanism of composite membrane, respectively. Overall, the combination of photocatalytic self-cleaning, anti-oil adhesion, and antibacterial effect renders the membrane high permeability and multiple-antifouling performance, which provides a new strategy for dealing with complex oily wastewater in petrochemical industry.

Application of role reversal and standardized patient simulation (SPS) in the training of new nurses.

PURPOSE: To explore the effect of role reversal and standardized patient simulation on the training of new nurses. METHOD: This study was conducted in a territory hospital in China between August 2021 and August 2022. The selected staff were all newly recruited and trained nurses, with a total of 58 cases. This study is a randomised controlled trial. The selected nurses were randomly divided into two groups. One group of 29 nurses (the control group) received routine training and assessment; the other group (the experimental group) was given role reversal combined with a standardized vertebral patient training examination. The implementation effects of different training and assessment methods were compared and analysed. RESULTS: Before the training, the core competence scores of nurses in the two groups were lower, and there was no significant data difference (P > 0.05). After training, the core competence scores of nurses were improved, and the score of nurses in the experimental group was 165.49 ± 22.34. The difference was statistically significant when compared with the score of nurses in the control group (P < 0.05), indicating that nurses in the experimental group had better abilities. At the same time, the satisfaction of the two groups of nurses with the training was 96.55% (experimental group) and 75.86% (control group), and the difference in data was significant (P < 0.05). The satisfaction of the experimental group of nurses was higher, and the training effect was better. CONCLUSION: In the training of new nurses, the combined application of role interchange and standardized patient training and assessment methods has significant effects, which can improve the core competency of nurses and improve the training satisfaction of nurses, which is significant.

Extracellular Domains of CAR Reprogram T-Cell Metabolism Without Antigen Stimulation.

Metabolism is an indispensable part of T-cell proliferation, activation, and exhaustion, yet the metabolism of chimeric antigen receptor (CAR)-T cells remains incompletely understood. CARs are comprised of extracellular domains that determine cancer specificity, often using single-chain variable fragments (scFvs), and intracellular domains that trigger signaling upon antigen binding. Here we show that CARs differing only in the scFv reprogram T-cell metabolism differently. Even in the absence of antigens, some CARs increase proliferation and nutrient uptake in T cells. Using stable isotope tracers and mass spectrometry, we observe basal metabolic fluxes through glycolysis doubling and amino acid uptake overtaking anaplerosis in CAR-T cells harboring rituximab scFv, unlike other similar anti-CD20 scFvs. Disparate rituximab and 14g2a-based anti-GD2 CAR-T cells are similarly hypermetabolic and channel excess nutrients to nitrogen overflow metabolism. Since CAR-dependent metabolic reprogramming alters cellular energetics, nutrient utilization, and proliferation, metabolic profiling should be an integral part of CAR-T cell development.

The effects of a low carbohydrate diet combined with partial meal replacement on obese individuals.

OBJECTIVE: We explored the dietary effects of replacing normal dietary staple foods with supplementary nutritional protein powder, dietary fiber, and fish oil on several metabolic parameters. We examined weight loss, glucose and lipid metabolism, and intestinal flora in obese individuals when compared with individuals on a reduced staple food low carbohydrate diet. METHODS: From inclusion and exclusion criteria, 99 participants (28 kg/m2 ≤ body mass index (BMI) ≤ 35 kg/m2) were recruited and randomly assigned to control and intervention 1 and 2 groups. Physical examinations and biochemical indices were performed/gathered before the intervention and at 4 and 13 weeks post intervention. After 13 weeks, feces was collected and 16s rDNA sequenced. RESULTS: After 13 weeks, when compared with controls, body weight, BMI, waist circumference, hip circumference, systolic blood pressure, and diastolic blood pressure values in intervention group 1 were significantly reduced. In intervention group 2, body weight, BMI, waist circumference, and hip circumference were significantly reduced. Triglyceride (TG) levels in both intervention groups were significantly reduced. Fasting blood glucose, glycosylated hemoglobin, glycosylated albumin, total cholesterol, and apolipoprotein B levels in intervention group 1 were decreased, while high density lipoprotein cholesterol (HDL-c) decreased slightly. Glycosylated albumin, TG, and total cholesterol levels in intervention group 2 decreased, while HDL-c decreased slightly, High sensitive C-reactive protein, MPO, Ox-LDL, LEP, TGF-ß1, IL-6, GPLD1, pro NT, GPC-4, and LPS levels in both intervention groups were lower when compared with controls. Adiponectin (ADPN) levels in intervention groups were higher when compared with controls. Tumor necrosis factor-α (TNF-α) levels in intervention group 1 were lower when compared with controls. There is no obvious difference in α diversity and ß diversity between intestinal flora of 3 groups. Among the first 10 species of Phylum, only the control group and the intervention group 2 had significantly higher Patescibacteria than the intervention group 1. Among the first 10 species of Genus, only the number of Agathobacter in intervention group 2 was significantly higher than that in control group and intervention group 1. CONCLUSIONS: We showed that an LCD, where nutritional protein powder replaced some staple foods and dietary fiber and fish oil were simultaneously supplemented, significantly reduced weight and improved carbohydrate and lipid metabolism in obese individuals when compared with an LCD which reduced staple food intake.

Rational Protein Design Yields a CD20 CAR with Superior Antitumor Efficacy Compared with CD19 CAR.

Chimeric antigen receptors (CAR) are fusion proteins whose functional domains are often connected in a plug-and-play manner to generate multiple CAR variants. However, CARs with highly similar sequences can exhibit dramatic differences in function. Thus, approaches to rationally optimize CAR proteins are critical to the development of effective CAR T-cell therapies. Here, we report that as few as two amino-acid changes in nonsignaling domains of a CAR were able to significantly enhance in vivo antitumor efficacy. We demonstrate juxtamembrane alanine insertion and single-chain variable fragment sequence hybridization as two strategies that could be combined to maximize CAR functionality, and describe a CD20 CAR that outperformed the CD19 CAR in antitumor efficacy in preclinical in vitro and in vivo assays. Precise changes in the CAR sequence drove dramatically different transcriptomic profiles upon antigen stimulation, with the most efficacious CAR inducing an enrichment in highly functional memory T cells upon antigen stimulation. These findings underscore the importance of sequence-level optimization to CAR T-cell function, and the protein-engineering strategy described here may be applied to the development of additional CARs against diverse antigens. See related Spotlight by Scheller and Hudecek, p. 142.

A cross-sectional study of the interaction between night shift frequency and age on hypertension prevalence among female nurses.

Night shift is a common work schedule. This study aimed to analyze the interaction between age and frequency of night shift on the hypertension prevalence. A census questionnaire was conducted in 512 medical institutions in 11 cities of Hebei Province. One lakh twenty-one thousand nine hundred three female nurses were included in this study. Binary Logistic regression analysis was done by SPSS Version 26.0. The youngest age group without night shift was used as the reference group. The odds ratio was calculated by different combinations of interaction items. Interaction coefficients were calculated by an Excel table designed by Andersson. Compared with the 18-25 year old ones without night shift, there existed an additive interaction between the age of 36-45 and more than 5-10 night shifts per month on hypertension prevalence. Odds ratio, the relative excess risk of interaction, the attributable proportion of interaction, and the synergy index and their 95% confidence intervals were 2.923(2.292-3.727), 0.631(0.309-0.954), 0.216(0.109-0.323), 1.488(1.158-1.913). Additive interaction was also found between the age of 36-45 and more than 10 night shifts per month. OR, RERI, API, SI, and their 95% confidence intervals were 3.430(2.273-5.175) 1.037(0.061-2.013), 0.303(0.089-0.516), and 1.746(1.093-2.788). There also existed an additive interaction between the age of 46-65 and more than 5-10 night shifts per month on hypertension prevalence. OR, RERI, API, SI, and their 95% confidence intervals were 7.398(5.595-9.781) 1.809(0.880-2.739), 0.245(0.148-0.341), and 1.394(1.199-1.622).There existed interaction between specific age groups and night shift frequency on the prevalence of hypertension among female nurses.

Verification of a cryptic t(Y;15) translocation in a male with an apparent 45,X karyotype.

BACKGROUND: A rare disease is that an individual with a non-chimeric karyotype of 45,X develops into a male. We explored the genetic aetiology of an infertile male with an apparent 45,X karyotype, which was subsequently verified as cryptic translocation between chromosomes Y and 15. METHODS: DNA was extracted from the patient's peripheral blood. A range of genetic testing was performed, including conventional chromosomal karyotyping, short tandem repeat (STR) analysis for azoospermia factor (AZF) region, fluorescence in situ hybridization (FISH) with specific probes groups of DXZ1/DYZ3, DYZ3/D15Z1/PML and SRY/D15Z1/PML, and chromosomal microarray analysis (CMA) for genomic copy number variations (CNVs). RESULTS: The patient was found to have an apparent 45,X karyotype. STR analysis showed that he possessed a short arm of the Y chromosome, including the SRY gene; however, he was missing the long arm of the Y chromosome, including AZFa + b + c and Yqter. A FISH assay of DXZ1 and DYZ3 probes showed a green signal of the X centromere and a red of the Y centromeric signal on a D-group-sized chromosome. By FISH assaying with D15Z1 and DYZ3 probes, chromosomes 15 and Y centromeric signals appeared closely on a single chromosome, as the PML control probe ascertained. A further FISH assay with D15Z1 and SRY probes revealed a signal of the SRY gene at the end of one arm of chromosome 15. The result of the CMA indicated a deletion with an approximate size of 45.31 Mb spanning from Yq11 to Yter. CONCLUSION: Our study enriched the karyotype-phenotype correlation of Y and 15 chromosomes translocation. It strengthened the critical roles of molecular genetic techniques in identifying the chromosomal breakpoints and regions involved. Genetic aetiology can guide early intervention in childhood and assisted reproduction in adulthood.

Bi-functional super-hydrophilic/underwater super-oleophobic 2D lamellar Ti3C2Tx MXene/poly (arylene ether nitrile) fibrous composite membrane for the fast purification of emulsified oil and photodegradation of hazardous organics.

Developing the multi-functional membranes including oil/water emulsion separation and removal of hazardous organic pollutants is essential to the purification of the complicated wastewater. However, it remains a daunting challenge to combine these intended functions while maintaining high separation efficiency. Herein, we developed a new 2D lamellar MXene/poly (arylene ether nitrile) (PEN) fibrous composite membrane through the self-assembly of TiO2 nanoparticles intercalated MXene nanosheets onto the porous PEN nanofibrous mats and bioinspired polydopamine triggered chemical-crosslinking with polyethyleneimine (PEI). Such nano-intercalation and mussel-inspired crosslinking could effectively regulate the interlayer spacing of the MXene nanosheet skin layer and surface wettability of the composite membrane, which also further contributed to the fast separation and unique bifunctional feature. It was found that the MXene@TiO2/PEN fibrous composite membrane exhibited low oil-adhesion and superhydrophilic (WCA = 0°)/underwater superoleophobic (UOCA > 155°) properties, which could efficiently separate various surfactant-stabilized oil-in-water emulsions under low pressure of 0.04 MPa while keeping good stability (Under 1 M HCl and 2 M NaOH solutions) and recyclability. Interestingly, the fibrous composite membrane achieved favorable permeation flux of 908-1003 Lm-2h-1 (2270-2507.5 Lm-2h-1bar-1) in comparison to other reported MXene based multifunctional composite membranes. Moreover, owing to the synergistic effect of MXene nanosheets and TiO2 nanoparticles, the MXene@TiO2/PEN membrane showed excellent photocatalytic degradation performance for various dyes under visible light, i.e. the photocatalytic degradation efficiency for 15 ppm MB, MO, CV, and MeB solutions achieved 92.31%, 93.50%, 98.06%, and 99.30% within 60 min, respectively. Such 2D MXene bio-functional composite membranes with outstanding oil/water emulsions separation and photocatalytic degradation of dyes pave an avenue for treating complicated oily wastewater.

Prenatal Diagnosis of Holt-Oram Syndrome With a Novel Mutation of TBX5 Gene: A Case Report.

Background: Holt-Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene. Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G>A) in the fetus inherited from the father. The variant (c.510+1G>A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China. Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.

The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice.

BACKGROUND: γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut peptide (WP) contains high levels of arginine, aspartic acid, and glutamate, and has been shown to improve cognitive deficits and memory impairment in mice, while restoring antioxidant enzyme levels and reducing brain inflammatory mediators. METHODS: This study investigated the effects of GABA and WP, either alone or in combination, on sleep disturbances in mice. The pentobarbital-prolonged sleep test, pentobarbital-threshold sleep test, and barbital-induced sleep test were conducted to assess the effects of GABA and WP on sleep quality by gavage for 30 days as follows: GABA (102.25 mg/kg), WP (102.25 mg/kg), GABA (33.95, 102.25, 306.75 mg/kg)/WP (102.25 mg/kg) mixture. Furthermore, neurotransmitter tests were performed using mice brain tissue to investigate the possible mechanisms of GABA and WP on sleep status. RESULTS: The results showed that the combined use of GABA and WP significantly increased sleep duration compared with single administration of either WP or GABA. Increasing doses of GABA in mice treated with combined GABA and WP elevated the sleep rate to 50.00%, 64.28%, and 64.28%, respectively, compared to mice treated with GABA alone (35.71%) or mice treated with WP alone (28.57%). In mice that received a combination of GABA and WP orally, the latency time was significantly decreased after 30 days compared to control mice (P<0.05). Additionally, in mice treated with GABA, WP, or the combination of GABA and WP, the concentrations of GABA and acetylcholine (Ach) in the brain were significantly elevated and the concentration of serotonin (5-HT) was decreased compared to untreated mice. CONCLUSIONS: These results demonstrated that the combined administration of GABA and WP could prolong the sleep duration, increase sleep rate, and shorten the sleep latency more effectively than the administration of either GABA or WP alone. The mechanisms of action may be related to the regulation of neurotransmitters in the brain tissue by the combination of GABA and WP.

2+0 CYP21A2 deletion carrier - a limitation of the genetic testing and counseling: A case report.

BACKGROUND: CYP21A2 gene mutations may all cause reduction or loss of 21-hydroxylase activity, leading to development of congenital adrenal hyperplasia (CAH) with different clinical phenotypes. For families with CAH children, genetic testing of the parents and genetic counseling are recommended to assess the risk of recurrence. CASE SUMMARY: We report a case of CAH with a high suspicion before delivery. The risk of the child suffering from CAH during the pregnancy had been underestimated due to the deviation of genetic counseling and genetic testing results. Our report confirmed a CYP21A2 homozygous deletion in this case, CYP21A2 heterozygous deletion in the mother, and a rare 2+0 CYP21A2 deletion in the father. CONCLUSION: It is important to analyze the distribution of CYP21A2 gene in the two alleles of parents of children with CAH.

L-theanine and Neumentix mixture improves sleep quality and modulates brain neurotransmitter levels in mice.

BACKGROUND: L-theanine (L-THE), a natural amino acid found in green tea, has been shown to improve anxiety and sleep. Neumentix proprietary spearmint extract (PSE), which is commonly found in beverage flavoring a pharmaceutical, also has a wide range of health benefits, including cognitive performance improvement. METHODS: Four experiments tested the effects of L-THE and PSE on sleep: a direct sleeping test, pentobarbital-induced sleeping test, sub-hypnotic pentobarbital-induced sleeping test, and sodium barbital-induced sleeping test. Presence of neurotransmitters in brain tissue was detected by liquid chromatography mass spectroscopy (HP LC-MS) during these studies. RESULTS: Pentobarbital-induced sleeping and sodium barbital-induced sleeping tests examined the potential effect of L-THE/PSE mixture on synergistic sleep, while neurotransmitter levels in the brain were determined by the high performance liquid chromatography/mass spectroscopy (HPLC/MS) method. L-THE and L-THE/PSE mixture showed increased sleep duration and shortened sleep latency when co-administrated with pentobarbital or sodium barbital. The mixture also increased sleeping rate when co-administrated with the pentobarbital at sub-hypnotic dose. Additionally, the L-THE, PSE and L-THE/PSE mixture significantly increased the concentrations of acetylcholine (Ach), γ-aminobutyric acid (GABA), and decreased the concentration of serotonin (5-HT) in the brain. CONCLUSIONS: These data demonstrated that L-THE/PSE mixture regulates sleep disorders via the GABA receptor and neurotransmitter systems.

Effect of frequency and pattern of night shift on hypertension risk in female nurses: a cross-sectional study.

OBJECTIVES: Understanding the effect of night shift on hypertension risk in nurses is important to improve the health of nurses and ensure patient safety. This study aimed to evaluate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in female nurses. METHODS: This cross-sectional study constituted 84 697 female nurses in 13 cities in China. The main contents of the survey included SBP, DBP, the frequency and pattern of night shift, and some other factors that might be associated with hypertension. Logistic regression analyses were used to calculate ORs and 95% CIs to estimate the effect of the frequency and pattern of night shift on hypertension risk and the interaction of them in relation to hypertension risk. RESULTS: Having more than 5 to 10 or more than 10 night shifts per month were significantly more likely to be hypertensive (OR 1.19, 95% CI 1.10-1.28; OR 1.32, 95% CI 1.13-1.54), whereas having less than or equal to 5 night shifts per month was not (OR 1.05, 95% CI 0.95-1.16). The patterns of night shift were all associated with a higher probability of hypertension and participants engaging in rapidly rotating night shift had a lower OR (1.14) than those having slowly rotating night shift (1.23) and permanent night shift (1.46). No significant interaction was observed between the frequency and the pattern of night shift (Pinteraction = 0.281). CONCLUSION: The frequency and pattern of night shift were associated with hypertension risk in female nurses and no significant interaction was observed between them.

Whole exome sequencing identifies c.963T > A and c.492 + 1G > A mutations in REN responsible for autosomal recessive renal tubular dysgenesis.

AIM: This study was aimed to identify the potentially pathogenic gene variants that contribute to the etiology of the autosomal recessive renal tubular dysgenesis (RTD) in the aborted fetus. METHODS: Illumina infinium global screening array was used to analyze chromosome karyotype of the aborted fetus. The exomes of the aborted fetus and his parents were sequenced using the whole exome sequencing technology. The resulting variants from whole exome sequencing were filtered by basic and advanced biological information analysis and the candidate mutation was verified by Sanger sequencing. RESULTS: Trisomy in chromosome 10 was found in the aborted fetus. The exon heterozygous variant of c.963T > A (p.Y321X) (nonsense mutation) and intron heterozygous variant of c.492 + 1G > A (splicing site mutation) in REN was first identified and validated by Sanger sequencing. Moreover, the exon heterozygous variant of c.963T > A (p.Y321X) and intron heterozygous variant of c.492 + 1G > A was from the mother and father, respectively. CONCLUSION: Our results reported the novel exon heterozygous variant of c.963T > A (p.Y321X) and intron heterozygous variant of c.492 + 1G > A in REN may contribute to autosomal recessive RTD, expanding our understanding of the causally relevant mutations for this disorder.