Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.

Nanoplastics causes heart aging/myocardial cell senescence through the Ca2+/mtDNA/cGAS-STING signaling cascade.

BACKGROUND: Nanoplastics (NPs) are now a new class of pollutants widely present in the soil, atmosphere, freshwater and marine environments. Nanoplastics can rapidly penetrate cell membranes and accumulate in human tissues and organs, thus posing a potential threat to human health. The heart is the main power source of the body. But up to now, the toxicological effects of long-term exposure to nanoplastics on the heart has not been revealed yet. RESULTS: We evaluated the effects of long term exposure of nanoplastics on cardiac cell/tissue in vitro and in vivo model. Furthermore, we explored the molecular mechanism by which nanoplastics exposure causes myocardial cell senescence. Immunohistochemistry, indirect immunofluorescence and ELISA were performed to detect the effects of nanoplastics on heart aging. We found that nanoplastics were able to induce significant cardiac aging through a series of biochemical assays in vivo. In vitro, the effects of nanoplastics on cardiac cell were investigated, and found that nanoplastics were able to internalize into cardiomyocytes in time and dose-dependant manner. Further biochemical analysis showed that nanoplastics induces cardiomyocytes senescence by detecting a series of senescence marker molecules. Molecular mechanism research shows that nanoplastics may cause mitochondrial destabilization by inducing oxidative stress, which leads to the leakage of mtDNA from mitochondria into the cytoplasm, and then cytoplasm-localized mt-DNA activates the cGAS-STING signaling pathway and promotes inflammation response, ultimately inducing cardiomyocytes senescence. CONCLUSIONS: In this work, we found that nanoplastics exposure induces premature aging of heart. Current research also reveals the molecular mechanism by which nanoplastics induces cardiomyocyte senescence. This study laid the foundation for further studying the potential harm of nanoplastics exposure on heart.

Three-dimensional ordered macroporous design of heterogeneous cobalt-iron phosphides as oxygen evolution electrocatalyst.

Oxygen evolution reaction (OER) plays a key role in electrochemical conversion, which needs efficient and economical electrocatalyst to boost its kinetics for large-scale application. Herein, a bimetallic CoP/FeP2heterostructure with a three-dimensional ordered macroporous structure (3DOM-CoP/FeP2) was synthesized as an OER catalyst to demonstrate a heterogeneous engineering induction strategy. By adjusting the electron distribution and producing a lot of active sites, the heterogeneous interface enhances catalytic performance. High specific surface area is provided by the 3DOM structure. Additionally, at the solid-gas-electrolyte threephase interface, the electrocatalytic reaction exhibits good mass transfer.In situRaman spectroscopy characterization revealed that FeOOH and CoOOH reconstructed from CoP/FeP2were the true OER active sites. Consequently, the 3DOM-CoP/FeP2demonstrates superior OER activity with a low overpotentials of 300/420 mV at 10/100 mA cm-2and meritorious OER durability. It also reveals promising performance as the overall water splitting anode.

Niobium-doped conductive TiO-TiO2 heterostructure supported bifunctional catalyst for efficient and stable zinc-air batteries.

The development of highly active and durable nonprecious metal-based bifunctional electrocatalysts for oxygen reduction/evolution reaction (ORR/OER) is important for rechargeable zinc-air batteries. Herein, a three-dimensional conductive niobium-doped TiO-TiO2 heterostructure supported ZIF-67-derived Co-NC bifunctional catalyst was fabricated. In the Co-NC@Nb-TiOx catalyst, the Nb doping promoted the formation of TiO-TiO2 heterojunction support, enhanced its conductivity and stability and provided strong electron metal-support interaction between Co-NC and Nb-TiOx. Also, the supported Co-NC nanoparticles provided abundant active sites with excellent ORR/OER activity. Experimental analysis reveals that the high OER activity of Co-NC@Nb-TiOx can be attributed to the in-situ generated CoOOH species. It exhibits excellent ORR activity, as shown by its onset potential (0.95 V vs. RHE) and half-wave potential (0.86 V vs. RHE). Its OER overpotential at 10 mA cm-2 is 480 mV. The zinc-air battery realizes outstanding cycling stability over 225 h cycles tested at 10 mA cm-2. This work demonstrates the importance of designing highly stable metal oxide-supported catalysts in electrochemical energy conversion devices.

Incorporating charged Ag@MOFs to boost the antibacterial and filtration properties of porous electrospinning polylactide films.

Faced with the pollution caused by particulate matter (PM) in the air, the prevalence of infectious diseases, and the environmental burden by use of nondegradable polymers, the existing filter materials such as meltblown cloth of polypropylene cannot satisfactorily meet people's requirements. In this study, Ag nanoparticles were loaded onto ZIF-8 particles by impregnation reduction to prepare the positively charged Ag@ZIF-8. The porous fibrous membranes of Ag@ZIF-8 with polylactide (PLA) were manufactured by electrostatic spinning technology. Due to the inherently charged feature of Ag@ZIF-8 particles and the presence of pores on fibers, the prepared membranes showed a stable good filtration efficiency of over 97 % at different humidity (30-90%RH, relative humidity). Meanwhile, the presence of charge on Ag@ZIF-8 and the synergistic effects of Ag and ZIF-8 particles made the membranes exhibit good antibacterial effects. The width of the inhibition zone of 3 wt%Ag@ZIF-8/PLA membrane reached 1.33 mm for E. coli and 1.35 mm for S. aureus, respectively.

Manipulating Redox Kinetics using p-n Heterojunction Biservice Matrix as both Cathode Sulfur Immobilizer and Anode Lithium Stabilizer for Practical Lithium-Sulfur Batteries.

As an attractive high-energy-density technology, the practical application of lithium-sulfur (Li-S) batteries is severely limited by the notorious dissolution and shuttle effect of lithium polysulfides (LiPS), resulting in sluggish reaction kinetics and uncontrollable dendritic Li growth. Herein, a p-n typed heterostructure consisting of n-type MoS2 nanoflowers embedded with p-type NiO nanoparticles is designed on carbon nanofibers (denoted as NiO-MoS2 @CNFs) as both cathode sulfur immobilizer and anode Li stabilizer for practical Li-S batteries. Such p-n typed heterostructure is proposed to establish the built-in electric field across the heterointerface for facilitated the positive charge to reach the surface of NiO-MoS2 , meanwhile inherits the excellent LiPS adsorption ability of p-type NiO nanoparticles and catalytic ability of n-type MoS2 . As the anode matrix, the implementation of NiO-MoS2 heterostructure can prevent the growth of Li dendrites by enhancing the lithiophilicity and reducing local current density. The obtained Li-S full battery exhibits an ultra-high areal capacity over 7.3 mAh cm-2 , far exceeding that of current commercial Li-ion batteries. Meanwhile, a stable cycling performance can be achieved under low electrolyte/sulfur ratio of 5.8 µL mg-1 and negative/positive capacity ratio of 1. The corresponding pouch cell maintains high energy density of 305 Wh kg-1 and stable cycling performance under various bending angles.

Weight loss and all-cause mortality: A propensity score matching cohort study.

BACKGROUND: Weight loss was supposed to help with decreasing risk of premature mortality. However, results on this topic remain debatable and limited by study design. OBJECTIVE: The present study aimed to investigate the association between weight loss and all-cause mortality among US adults with overweight or obesity in a national cohort study by using propensity score matching (PSM) analysis. METHODS: A total of 5486 pairs of participants were matched in the National Health and Nutrition Examination Survey (NHANES, 2003-2015) after PSM. Hazard ratios (95% confidence intervals) (HRs (95% CIs)) were employed to evaluate the association between weight loss indicated by long-term weight loss (LTWL) and all-cause mortality by using Cox proportional hazards regression models. RESULTS: During a median follow-up of 6.8 years, 674 participants died from all-cause mortality. In each PSM match, compared with participants with LTWL < 5%, the HRs (95% CIs) for participants with LTWL of 5-9.9% (2877 pairs), 10-14.9% (1315 pairs), and ≥ 15% (1294 pairs) were 1.18 (0.83-1.68) (P = 0.366), 1.65 (1.17-2.34) (P = 0.005), and 1.91 (1.21-3.00) (P = 0.006), respectively. The significant increased risk of all-cause mortality for LTWL ≥ 15% remained among male, female, participants aged ≥ 65 years, without weight loss intention, with non-communicable diseases, and without exceeding estimated energy requirement. CONCLUSION: Weight loss especially for being ≥ 15% should be cautious for US adults with overweight or obesity.

Serum urea acid and urea nitrogen levels are risk factors for maternal and fetal outcomes of pregnancy: a retrospective cohort study.

BACKGROUND: In recent years, results on the association between serum uric acid (UA) and pregnancy outcomes have been inconsistent, and the association between urea nitrogen (UN) and adverse pregnancy outcomes in normal pregnant women has not been reported. Thus, we examined the association of UA and UN levels during gestation with the risk of adverse pregnancy outcomes in a relatively large population. METHODS: A total of 1602 singleton mothers from Union Shenzhen Hospital of Huazhong University of Science and Technology at January 2015 to December 2018 were included. Both UA and UN levels were collected and measured during the second (16-18th week) and third (28-30th week) trimesters of gestation respectively. Statistical analysis was performed using multivariate logistic regression. RESULTS: After adjustment, the highest quartile of UA in the third trimester increased the risk of premature rupture of membranes (PROM) and small for gestational age infants (SGA) by 48% (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.04-2.10) and 99% (95% CI: 1.01-3.89) compared to those in the lowest quartile. The adjusted OR (95% CI) in the highest quartile of UN for the risk of SGA was 2.18 (95% CI: 1.16-4.13) and 2.29 (95% CI: 1.20-4.36) in the second and third trimester, respectively. In the second trimester, when UA and UN levels were both in the highest quartile, the adjusted OR (95% CI) for the risk of SGA was 2.51 (95% CI: 1.23-5.10). In the third trimester, when the group 1 (both indicators are in the first quartile) was compared, the adjusted ORs (95% CI) for the risk of SGA were 1.98 (95% CI: 1.22-3.23) and 2.31 (95% CI: 1.16-4.61) for group 2 (UA or UN is in the second or third quartile) and group 3 (both indicators are in the fourth quartile), respectively. CONCLUSIONS: Higher UA and UN levels increased the risk of maternal and fetal outcomes. The simultaneous elevation of UA and UN levels was a high-risk factors for the development of SGA, regardless of whether they were in the second or third trimester.

Adverse pregnancy outcomes are important public health problems in terms of high mortality and long-term health effects of maternal and newborn babies. This study assessed the association between serum urea acid and urea nitrogen levels during pregnancy and the risk of adverse pregnancy outcomes in Chinese women. The study was conducted between January 2015 and December 2018. Serum uric acid and urea nitrogen were measured at weeks 16­18 and 28­30, respectively. A total of 1602 singleton pregnant women participated in the study. We found that elevated levels of uric acid and urea nitrogen increased the risk of maternal and infant outcomes. In addition, we found for the first time that elevated uric acid and urea nitrogen concentrations were a risk factor for SGA, both in the second and third trimesters. Therefore, monitoring maternal uric acid and urea nitrogen biochemical parameters during pregnancy is necessary to optimize nursing and intervention. Furthermore, uric acid and urea nitrogen are simple, inexpensive, and readily available tests and should be evaluated additionally.

Association Between Serum Ferritin Concentration and Risk of Adverse Maternal and Fetal Pregnancy Outcomes: A Retrospective Cohort Study.

Objective: This study evaluated the associations of serum ferritin (SF) concentration during pregnancy with the risk of adverse maternal and fetal pregnancy outcomes. Methods: We conducted a retrospective study of 2327 pregnant women from 2015 to 2020 in Guangdong, China. SF concentrations were measured at 16-18th and 28-32th week of gestation. Logistic regression models were applied to estimate the association between SF concentration and the risk of adverse pregnancy outcomes. Results: After multivariable adjustment, the odds ratio (OR) of the highest quartile of SF concentration at 16-18th week of gestation was 1.43 (95% confidence interval [CI]: 1.09, 1.89) for gestational diabetes mellitus (GDM) and 1.79 (95% CI: 1.15, 2.79) for small for gestational age (SGA) when compared with the lowest quartile. At 28-32th week of gestation compared with the lowest quartile, women with SF in the highest quartile had an increased risk of SGA (OR: 1.62; 95% CI: 1.01, 2.62). Moreover, the lowest quartile of SF concentration decreased risk of SGA by 90% (95% CI: 0.01, 0.80) when compared with the highest quartile among pregnancy women with GDM. Conclusion: Elevated SF concentrations increased the risk of GDM and SGA during pregnancy. Maintaining an appropriately low level of maternal SF at 28-32th week of gestation in women with GDM could reduce the risk of SGA.

Procyanidins and its metabolites by gut microbiome improves insulin resistance in gestational diabetes mellitus mice model via regulating NF-κB and NLRP3 inflammasome pathway.

Gestational Diabetes Mellitus (GDM) has an effect on the health of pregnant women and fetuses. Procyanidins (PA) is a flavonoid with anti-diabetic activity, but its effects and mechanisms on GDM have not been defined. Herein, we studied further the functions and mechanisms of PA on insulin resistance (IR) in GDM mice, as well as on postpartum and offspring mice. GDM mice model was built by feeding a high-fat-high-sucrose diet, and PA intervention (27.8 mg/kg/d) was performed from 4 weeks before pregnancy to delivery. Intestinal flora deficient (IFD) mice model was established by broad spectrum antibiotics. PA decreased the gestational weight gain, and the levels of fasting blood glucose, insulin, homeostasis model of assessment for IR index, yet increased the levels of HOMA for insulin sensitivity index. Interestingly, in IFD mice the effect of PA on improving IR was significantly weakened. PA inhibited inflammation by decreasing the levels of IL-6, TNF-α, IL-17 and CRP, which also been blocked in the IFD mice. Moreover, PA improved glycometabolism and reduced the secretion of inflammatory factors and hepatic inflammation infiltration of mice at 4 weeks postpartum, but had no significant effect on offspring mice. Mechanistically, PA treatment suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome activation. In vitro studies, 4-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl) propionic acid, main intestinal flora metabolites of PA restrained NF-κB/NLRP3 activation. In conclusions, PA improved IR via NF-κB/NLRP3 pathway in GDM and postpartum mice, which partly through its metabolites by gut microbiome.

Fructose Induces Insulin Resistance of Gestational Diabetes Mellitus in Mice via the NLRP3 Inflammasome Pathway.

Background: Insulin resistance (IR), which is affected by dietary factors, is the main pathology underlying of gestational diabetes mellitus (GDM). Fructose (Fru), a sugar found in fruits, honey, and food sweeteners, has been reported to induce IR and inflammation. This study explored the effects and mechanisms of Fru on IR of GDM in pregnant and postpartum mice and their offspring. Methods: The 6-week-old female C57BL/6J mice were randomly divided into control (Chow) and fructose (Fru) groups, with the latter receiving 20% (w/v) Fru in drinking water from 2 weeks before pregnancy to the end of pregnancy. The effects of Fru on IR and inflammation were determined using serum parameters, glucose metabolism tests, immunohistochemistry, and western blotting. Results: Compared with the Chow group mice, pregnant mice treated with Fru exhibited greater gestational weight gain, higher fasting blood glucose and insulin concentrations, and a higher homeostasis model of assessment (HOMA) for IR index, but a lower HOMA for insulin sensitivity index. Treatment with Fru also increased the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-17, and C-reactive protein in sera and the expression of IL-6, TNF-α, IL-17, and IL-1ß mRNA in liver tissues of pregnant mice. Both CD68 and IL-1ß positive cell were increased in Fru-treated mice compared with in Chow mice. Fru treatment also promoted IR and inflammation in mice at 4 weeks after delivery and in offspring mice. Mechanistically, Fru promoted the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 to activate the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Conclusions: Exposure to Fru before and during pregnancy induced IR in pregnant mice, which continued at 4 weeks postpartum and affected the offspring. The effects of Fru may be associated with activation of the NF-κB-NLRP3 pathway.

High hemoglobin level is a risk factor for maternal and fetal outcomes of pregnancy in Chinese women: A retrospective cohort study.

BACKGROUND: To examine the association of hemoglobin (Hb) levels during gestation with the risk of selected adverse pregnancy outcomes such as preterm birth (PTB), low-birth-weight infants (LBW) and small-for-gestational-age infants (SGA) in Chinese women. METHODS: This retrospective cohort study was conducted in the Department of Gynecology and Obstetrics at the Union Shenzhen Hospital of the Huazhong University of Science and Technology, using routinely collected maternity and hospital data on pregnancies (2015-2018). Hb levels were measured during the second (16-18th weeks) and third (28-30th weeks) trimesters of pregnancy, and pregnancy outcomes were recorded in the hospital information system. Hb levels were categorized into four groups as follows: < 110 g/L, 110-119 g/L, 120-130 g/L, and > 130 g/L. The second group (Hb 110-119 g/L) was defined as the reference group. Statistical analysis was performed using multivariate logistic regression. RESULTS: A total of 1911 singleton mothers were included. After multivariable adjustment, Hb levels > 130 g/L in the second trimester increased the risk of LBW (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.12-5.76). In the third trimester of gestation, compared with women whose Hb levels between 110 and 119 g/L, women with Hb levels > 130 g/L had an increased risk of LBW (OR, 2.20; 95% CI, 1.07-4.51) and SGA (OR, 2.00; 95% CI, 1.05-3.80). When we compared the highest and lowest quartiles of changes in the Hb across the second and third trimesters, the adjusted ORs were 0.35 (95% CI: 0.18-0.68) for PTB and 0.47 (95% CI: 0.23-0.98) for LBW. CONCLUSION: Maternal Hb > 130 g/L was associated with increased risk of adverse pregnancy outcomes. Reduction of the risks of PTB and SGA were observed with the appropriate increase of Hb level during the third trimester.

Synergistic Binary Fe-Co Nanocluster Supported on Defective Tungsten Oxide as Efficient Oxygen Reduction Electrocatalyst in Zinc-Air Battery.

Rational design of metal oxide supported non-precious metals is essential for the development of stable and high-efficiency oxygen reduction reaction (ORR) electrocatalysts. Here, an efficient ORR catalyst consisting of binary Fe/Co nanoclusters supported by defective tungsten oxide and embedded N-doped carbon layer (NC) with a 3D ordered macroporous architecture (3DOM Fe/Co@NC-WO2- x ) is developed. The oxygen deficient 3DOM WO2- x not only serves as a porous and stable support, but also enhances the conductivity and ensures good dispersion of the binary Fe/Co nanocluster, benefiting its ORR catalytic activity. Theoretical calculation shows that there exists a synergistic effect of electron transfer from Fe to Co in the supported binary Fe/Co cluster, promoting the ORR reaction energetics. Accordingly, the 3DOM Fe/Co@NC-WO2- x catalyst exhibits excellent ORR activity in alkaline medium with a half wave potential (E1/2 ) of 0.87 V higher than that of Pt/C (0.85 V). The zinc-air batteries assembled by 3DOM Fe/Co@NC-WO2- x cathode deliver a higher power density and specific capacity than that of Pt/C. A new strategy of combining synergistic binary-metal nanoclusters and conductive metal oxide support design is provided here to develop efficient and durable ORR electrocatalyst.

Ultrathin Superhydrophobic Flexible Tactile Sensors for Normal and Shear Force Discrimination.

Flexible tactile sensors, with the ability to sense and even discriminate between different mechanical stimuli, can enable real-time and precise monitoring of dexterous and complex robotic motions. However, making them ultrathin and superhydrophobic for practical applications is still a great challenge. Here, superhydrophobic flexible tactile sensors with hierarchical micro- and nanostructures, that is, warped graphene nanosheets adhered to micron-height wrinkled surfaces, were constructed using ultrathin medical tape (40 µm) and graphene. The tactile sensor enables the discrimination of normal and shear forces and senses sliding friction and airflow. Moreover, the tactile sensor exhibits high sensitivity to normal and shear forces, extremely low detection limits (15 Pa for normal forces and 6.4 mN for shear forces), and cyclic robustness. Based on the abovementioned characteristics, the tactile sensor enables real-time and accurate monitoring of the robotic arm's motions, such as moving, gripping, and lifting, during the process of picking up objects. The superhydrophobicity even allows the sensor to monitor the motions of the robotic arm underwater in real time. Our tactile sensors have potential applications in the fields of intelligent robotics and smart prosthetics.

Conductive Al-Doped ZnO Framework Embedded with Catalytic Nanocages as a Multistage-Porous Sulfur Host in Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries possess many practical challenges including the lithium polysulfide (LiPS) "shuttle effect" and their sluggish conversion kinetics. To address these issues, a unique hierarchical porous architecture, combining highly conductive ordered macroporous skeleton and embedded microporous particles is rationally designed as a dual-effective polysulfide immobilizer and conversion promoter. In this nanoporous architecture, Al-doped ZnO (AZO) acts as a conductive macroporous framework, profiting chemical anchoring of LiPS as well as facilitating electrolyte infiltration and ion diffusion; Co nanoparticle-anchored N-doped carbon (Co-NC) derived from CoZn-metal-organic framework is embedded in the macropores to further strengthen the LiPS adsorption, catalytically accelerating conversion kinetics of LiPS simultaneously. Consequently, the Co-NC@AZO/S cathode delivers a notable rate capability of 635.5 mA h g-1 at 5 C. A high area capacity of about 5.8 mA h cm-2 with a mass loading of 6.8 mg cm-2 is also achieved under a lean electrolyte (E/S = 5.7). Additionally, the Li-S pouch cells equipped with Co-NC@AZO can be extended to sulfur loading as high as 4.0 mg cm-2, delivering a superb capability of 897.5 mA h g-1 after 100 cycles. This work puts forward a design for stably cycled and practically viable Li-S batteries.

Antidepressant effects of total iridoids of Valeriana jatamansi via the intestinal flora-blood-brain barrier pathway.

CONTEXT: Valeriana jatamansi Jones [syn. V. wallichii DC, (Valerianaceae)] (VJJ) is used to treat depression. OBJECTIVE: To explore the effects of total iridoids of VJJ extract (TIV) on chronic unpredictable mild stress (CUMS) in mice. MATERIALS AND METHODS: VJJ roots and rhizomes were extracted with 70% ethanol. CUMS rats were treated daily with fluoxetine (2.6 mg/kg, i.g.) or TIV (5.7, 11.4, and 22.8 mg/kg, i.g.) for 14 days. Male Kun Ming mice on normal chow and 0.5% CMC-Na solution were used as a control. Behavioural tests included the tail suspension (TST) and sucrose preference tests (SPT). Evans blue staining was used to evaluate blood-brain barrier (BBB) permeability. Western blotting was used to measure zonula occludens-1 (ZO-1) and occludin expression. 16S rRNA sequencing was used to analyse intestinal flora abundance. Tax4Fun was used to predict KEGG metabolic pathways. RESULTS: TIV treatment reduced TST time (117.35 ± 8.23 or 108.95 ± 6.76 vs. 144.45 ± 10.30 s), increased SPT (55.83 ± 7.24 or 53.12 ± 13.85 vs. 38.98 ± 5.43%), increased the abundance of phylum Firmicutes (86.99 ± 0.03 vs. 60.88 ± 0.19%) and genus Lactobacillus (75.20 ± 0.19 vs. 62.10 ± 0.13%), reduced the abundance of phylum Bacteroidetes (6.69 ± 0.06 or 11.50 ± 0.09 vs. 25.07 ± 0.20%). TIV increased carbohydrate metabolism (14.50 ± 3.00 × 10-3 or 14.60 ± 2.00 × 10-3 or 14.90 ± 2.00 × 10-3 vs.13.80 ± 4.00 × 10-3%), replication and repair functions (5.60 ± 1.00 × 10-3 or 5.60 ± 1.00 × 10-3 vs. 5.10 ± 4.00 × 10-3%), reduced the frequency of infectious disease (1.60 ± 2.00 × 10-4 or 1.90 ± 5.00 × 10-4 or 1.80 ± 3.00 × 10-4 vs. 2.20 ± 7.00 × 10-3%), BBB permeability (0.77 ± 0.30 vs. 1.81 ± 0.33 µg/g), and up-regulated the expression of ZO-1 (1.42-fold, 1.60-fold, 1.71-fold) and occludin (1.79-fold, 2.20-fold). CONCLUSIONS: TIV may modulate the intestinal flora, thereby inducing the expression of ZO-1 and occludin, protecting the BBB and exerting an antidepressant effect.

IOAT: an interactive tool for statistical analysis of omics data and clinical data.

BACKGROUND: With the development of high-throughput sequencing technology, a huge amount of multi-omics data has been accumulated. Although there are many software tools for statistical analysis and visual development of omics data, these tools are not suitable for private data and non-technical users. Besides, most of these tools have specialized in only one or perhaps a few data typesare, without combining clinical information. What's more, users could not choose data processing and model selection flexibly when using these tools. RESULTS: To help non-technical users to understand and analyze private multi-omics data and ensure data security, we developed an interactive desk tool for statistical analysis and visualization of omics and clinical data (shortly IOAT). Our mainly targets csv format data, and combines clinical data with high-dimensional multi-omics data. It also contains various operations, such as data preprocessing, feature selection, risk assessment, clustering, and survival analysis. By using this tool, users can safely and conveniently try a combination of various methods on their private multi-omics data to find a model suitable for their data, conduct risk assessment and determine their cancer subtypes. At the same time, the tool can also provide them with references to genes that are closely related to tumor staging, facilitating the development of precision oncology. We review IOAT's main features and demonstrate its analysis capabilities on a lung from TCGA. CONCLUSIONS: IOAT is a local desktop tool, which provides a set of multi-omics data integration solutions. It can quickly perform a complete analysis of cancer genome data for subtype discovery and biomarker identification without security issues and writing any code. Thus, our tool can enable cancer biologists and biomedicine researchers to analyze their data more easily and safely. IOAT can be downloaded for free from https://github.com/WlSunshine/IOAT-software .

Changes in serum total bile acid concentrations are associated with the risk of developing adverse maternal and perinatal outcomes in pregnant Chinese women.

BACKGROUND AND AIMS: We aimed to investigate the association between total bile acid (TBA) concentrations changes during the second and third trimesters and the risk of developing adverse maternal and perinatal outcomes (AMPO). METHODS: A total of 1569 pregnant Chinese women were enrolled. Serum TBA concentrations were measured during the 16-18th and 29-34th weeks of gestation. Logistic regression models were performed. RESULTS: After multivariable adjustment, each standard deviation increase in the TBA concentrations in the second trimester was associated with a 30% (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.13, 1.50) increased risk of gestational diabetes mellitus (GDM) and a 22% (OR = 1.22, 95% CI: 1.07, 1.63) increased risk of premature rupture of membranes (PROM). When we compared the highest and lowest quartiles of changes in the TBA Z-scores across the second and third trimesters, the adjusted ORs were 1.84 (95% CI: 1.28, 2.65) for PROM and 1.47 (95% CI: 1.07, 2.28) for macrosomia. CONCLUSION: Elevated serum TBA concentrations during pregnancy were positively associated with increased risks of GDM and PROM. Women with more drastic changes in TBA concentrations across the second and third trimesters were at a higher risk of developing PROM and macrosomia.

Synthesis and Redox Properties of Water-Soluble Asymmetric Trityl Radicals.

Tetrathiatriarylmethyl (trityl) radicals have been recently shown to react with biological oxidoreductants including glutathione (GSH), ascorbic acid (Asc), and superoxide anion radical (O2•-). However, how the substituents affect the reactivity of trityl radicals is still unknown. In this work, five asymmetric trityl radicals were synthesized and their reactivities with GSH, Asc, and O2•- investigated. Under aerobic conditions, GSH induces fast decays for the thioether- (TSA) and N-methyleneglycine-substituted (TGA) derivatives and slow decay for the 4-carboxyphenyl-containing one (TPA). Under anaerobic conditions, the direct reduction of these radicals by GSH also occurs with rate constants (kGSH) from 1.8 × 10-4 M-1 s-1 for TPA to 1.0 × 10-2 M-1 s-1 for TGA. Moreover, these radicals can also react with O2•- with rate constants (kSO) from 1.2 × 103 M-1 s-1 for ET-01 to 1.6 × 104 M-1 s-1 for TGA. Surprisingly, these radicals are completely inert to Asc in both aerobic and anaerobic conditions. Additionally, the substituents exert an important effect on redox potentials of these trityl radicals. This work demonstrates that the redox properties of the trityl radicals strongly depend on their substituents, and TPA with high stability toward GSH shows great potential for intracellular applications.

Use of Surface Penetration Technology to Fabricate Superhydrophobic Multifunctional Strain Sensors with an Ultrawide Sensing Range.

Flexible sensors with wide sensing ranges require responsiveness under tiny and large strains. However, the development of strain sensors with wide detection ranges is still a great challenge due to the conflict between the tiny strain requirements of sparse conductive networks and the large strain requirement of dense conductive networks. Herein, we present a facile method for fabricating a gradient conductive network composed of sparse and dense conductive networks. The surface penetration technology in which carbon black (CB) penetrated from the natural rubber latex (NRL) glove surface to the interior was used to fabricate a gradient conductive network. The prolonged immersion time from 1 to 30 min caused the penetration depth of CB to increase from 2 to 80 µm. Moreover, CB formed hierarchical rough micro- and nanoscale structures, creating a superhydrophobic surface. The gradient conductive network of sensors produced an ultrawide detection range of strain (0.05-300%) and excellent reliability and reproducibility. The sensors can detect a wide range of human motions, from tiny (wrist pulse) to large (joint movements) motion monitoring. The flexible sensors attached to a flexible basement can be used to detect pressure in a wide detection range (1.7-2900 kPa). Pressure responsiveness was used to detect the weight, sound pressure, and dripping of tiny droplets. The sensor showed an excellent response to organic solvents, and the response intensity increased with the increasing swelling degree of the solvent for NRL.