Effects of gut bacteria and their metabolites on gut health of animals.

The intestine tract is a vital site for the body to acquire nutrients, serving as the largest immune organ. Intestinal health is crucial for maintaining a normal physiological state. Abundant microorganisms reside in the intestine, colonized in a symbiotic manner. These microorganisms can generate various metabolites that influence host physiological activities. Microbial metabolites serve as signaling molecules or metabolic substrates in the intestine, and some intestinal microorganisms act as probiotics and promote intestinal health. Researches on host, probiotics, microbial metabolites and their interactions are ongoing. This study reviews the effects of gut bacteria and their metabolites on intestinal health to provide useful references for animal husbandry.

The effects of parental retirement on adult children's health: Evidence from China.

Using representative data from China, we examine the causal effects of parental retirement on the health of adult children. To do so, we adopt a fuzzy regression discontinuity design and exploit the mandatory retirement ages in China as cut-off points. We find no evidence that parental retirement has significant effects on the mental health, healthcare utilization, or risky health behaviors of adult children. However, paternal retirement and maternal retirement have different effects on adult children's Self-reported health (SRH). Paternal retirement has a significantly negative effect only on the SRH of sons, while maternal retirement does not induce such effects. Potential mechanisms of intergenerational transfer through which parental retirement might affect adult children's health are also explored.

An Intelligent Graphene-Based Biosensing Device for Cytokine Storm Syndrome Biomarkers Detection in Human Biofluids.

Abnormal elevated levels of cytokines such as interferon (IFN), interleukin (IL), and tumor necrosis factor (TNF), are considered as one of the prognosis biomarkers for indicating the progression to severe or critical COVID-19. Hence, it is of great significance to develop devices for monitoring their levels in COVID-19 patients, and thus enabling detecting COVID-19 patients that are worsening and to treat them before they become critically ill. Here, an intelligent aptameric dual channel graphene-TWEEN 80 field effect transistor (DGTFET) biosensing device for on-site detection of IFN-γ, TNF-α, and IL-6 within 7 min with limits of detection (LODs) of 476 × 10-15 , 608 × 10-15 , or 611 × 10-15 m respectively in biofluids is presented. Using the customized Android App together with this intelligent device, asymptomatic or mild COVID-19 patients can have a preliminary self-detection of cytokines and get a warning reminder while the condition starts to deteriorate. Also, the device can be fabricated on flexible substrates toward wearable applications for moderate or even critical COVID-19 cases for consistently monitoring cytokines under different deformations. Hence, the intelligent aptameric DGTFET biosensing device is promising to be used for point-of-care applications for monitoring conditions of COVID-19 patients who are in different situations.

Medicaid expansion and the mental health of college students.

Reported mental health problems have risen dramatically among US college students over time, as has treatment for these problems. We examine the effect of state-level Medicaid expansion following the 2014 implementation of the Affordable Care Act on the diagnosis of mental health conditions, psychotropic prescription drug use, and the mental health status of a national sample of college students. We find that students from disadvantaged backgrounds are more likely to report being on public insurance after 2014 in expansion states relative to non-expansion states, while more advantaged students do not see this increase. Both diagnosis of common mental health conditions and psychotropic drug use increase following expansion for disadvantaged students relative to advantaged ones, which translates into an elimination of the pre-expansion gap in these outcomes by family background in expansion states. However, in contrast to some recent work on Medicaid expansion and mental health, we do not find that these changes are associated with improvements in self-reported mental health status. We also do not find that Medicaid expansion has affected risky health behaviors or academic outcomes.

An Ultraflexible and Stretchable Aptameric Graphene Nanosensor for Biomarker Detection and Monitoring.

An ultraflexible and stretchable field-effect transistor nanosensor is presented that uses aptamer-functionalized monolayer graphene as the conducting channel. Specific binding of the aptamer with the target biomarker induces a change in the carrier concentration of the graphene, which is measured to determine the biomarker concentration. Based on a Mylar substrate that is only 2.5-µm thick, the nanosensor is capable of conforming to underlying surfaces (e.g., those of human tissue or skin) that undergo large bending, twisting, and stretching deformations. In experimental testing, the device is rolled on cylindrical surfaces with radii down to 40 µm, twisted by angles ranging from -180° to 180°, or stretched by extensions up to 125%. With these large deformations applied either cyclically or non-recurrently, the device is shown to incur no visible mechanical damage, maintain consistent electrical properties, and allow detection of TNF-α, an inflammatory cytokine biomarker, with consistently high selectivity and low limit of detection (down to 5 × 10-12M). The nanosensor can thus potentially enable consistent and reliable detection of liquid-borne biomarkers on human skin or tissue surfaces that undergo large mechanical deformations.

Sensitive detection of lung cancer biomarkers using an aptameric graphene-based nanosensor with enhanced stability.

We present an electrolyte-gated graphene field effect transistor (GFET) nanosensor using aptamer for rapid, highly sensitive and specific detection of a lung cancer biomarker interleukin-6 (IL-6) with enhanced stability. The negatively charged aptamer folds into a compact secondary conformation upon binding with IL-6, thus altering the carrier concentration of graphene and yielding a detectable change in the drain-source current Ids. Aptamer has smaller size than other receptors (e.g. antibodies), making it possible to bring the charged IL-6 more closely to the graphene surface upon affinity binding, thereby enhancing the sensitivity of the detection. Thanks to the higher stability of aptamer over antibodies, which degrade easily with increasing storage time, consistent sensing performance was obtained by our nanosensor over extended-time (>24 h) storage at 25 °C. Additionally, due to the GFET-enabled rapid transduction of the affinity recognition to IL-6, detection of IL-6 can be achieved in several minutes (<10 min). Experimental results indicate that this nanosensor can rapidly and specifically respond to the change in IL-6 levels with high consistency after extended-time storage and a detection limit (DL) down to 139 fM. Therefore, our nanosensor holds great potential for lung cancer diagnosis at its early stage.

Olfactory dysfunction in the APP/PS1 transgenic mouse model of Alzheimer's disease: Morphological evaluations from the nose to the brain.

Olfactory dysfunction is among the signs of Alzheimer's disease (AD) and cognitive impairment. It has been demonstrated Aß was associated with olfactory impairment observed in both transgenic mice and in AD patients. In this study, we evaluated amyloid deposition in the olfactory circuit of APP/PS1 transgenic mouse model of AD, which showed olfactory dysfunction in olfactory behavior tests. We found amyloid depositions were widely distributed in the whole olfactory circuit. Moreover, we think these amyloid depositions contribute to neuronal atrophy, dendritic abnormalities, synapse loss and axonal degeneration. Therefore, there was a correlation between olfactory deficits and amyloid deposition. Our findings provide initial insights into the pathological basis of AD-related olfactory dysfunction.

[Gene Profile and Clinical Significance of Concomitant Mutations in CN-AML Patients with CEBPA Mutation].

OBJECTIVE: To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients. METHODS: 151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively. 34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology. The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared, and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed. RESULTS: In 151 patients with CN-AML, 55 (36.42%) were positive for CEBPA mutation (including 36 cases of CEBPAdm and 19 cases of CEBPAsm), of which 41 (74.55%) had co-mutations with other genes. The main mutated genes were GATA2 (25.45%, 14/55), TET2 (21.82%, 12/55), FLT3 (20.00%, 11/55), NRAS (12.73%, 7/55) and WT1 (9.09%, 9/55), etc. Some cases had two or more concomitant gene mutations. Grouping the mutant genes according to their functions showed that CEBPA+ group had lower mutation rates of histone methylation (P =0.002) and chromatin modification genes (P =0.002, P =0.033), and higher mutation rates of transcription factors (P =0.037) than CEBPA- group. In 55 patients with CEBPA+ CN-AML, the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group (P =0.005), the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group (P =0.003), and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group, respectively (P =0.002, P =0.008). DFS of CEBPA+ CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group (median DFS: 12 months vs not reached) (P =0.034). Compared with DNA methylation gene mutation-negative group, CEBPA+ CN-AML patients with DNA methylation gene mutation had lower CR rate (P =0.025) significantly shorter OS and DFS (median OS: 20 months vs not reached, P =0.006; median DFS: 15 months vs not reached, P =0.049). OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group (median OS: 12 months vs 40 months) (P =0.008). Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts (P =0.046), concomitant DNA methylation gene mutation (P =0.006) and histone methylation gene mutation (P =0.036) were independent risk factors affecting the prognosis. CONCLUSION: CN-AML patients with CEBPA mutation have specific concomitant gene profile, and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Monitoring Cd2+ in oily wastewater using an aptamer-graphene field-effect transistor with a selective wetting surface.

The discharge of oily industrial wastewater containing heavy metal ions with the development of industry severely threatens the environment and human health. Therefore, it is of great significance to monitor the concentration of heavy metal ions in oily wastewater quickly and effectively. Here, an integrated Cd2+ monitoring system consisting of an aptamer-graphene field-effect transistor (A-GFET), oleophobic/hydrophilic surface and monitoring-alarm circuits was presented for monitoring the Cd2+ concentration in oily wastewater. In the system, oil and other impurities in wastewater are isolated by an oleophobic/hydrophilic membrane before detection. The concentration of Cd2+ is then detected by a graphene field-effect transistor with a Cd2+ aptamer modifying the graphene channel. Finally, the detected signal is collected and processed by signal processing circuits to judge whether the Cd2+ concentration exceeds the standard. Experimental results demonstrated that the separation efficiency of the oleophobic/hydrophilic membrane to an oil/water mixture was up to 99.9%, exhibiting a high oil/water separation ability. The A-GFET detecting platform could respond to changes in the Cd2+ concentration within 10 min with a limit of detection (LOD) of 0.125 pM. The sensitivity of this detection platform to Cd2+ near 1 nM was 7.643 × 10-2 nM-1. Compared with control ions (Cr3+, Pb2+, Mg2+, Fe3+), this detection platform exhibited a high specificity to Cd2+. Moreover, the system could send out a photoacoustic alarm signal when the Cd2+ concentration in the monitoring solution exceeds the preset value. Therefore, the system is practical for monitoring the concentration of heavy metal ions in oily wastewater.

A closed-loop catalytic nanoreactor system on a transistor.

Precision chemistry demands miniaturized catalytic systems for sophisticated reactions with well-defined pathways. An ideal solution is to construct a nanoreactor system functioning as a chemistry laboratory to execute a full chemical process with molecular precision. However, existing nanoscale catalytic systems fail to in situ control reaction kinetics in a closed-loop manner, lacking the precision toward ultimate reaction efficiency. We find an inter-electrochemical gating effect when operating DNA framework-constructed enzyme cascade nanoreactors on a transistor, enabling in situ closed-loop reaction monitoring and modulation electrically. Therefore, a comprehensive system is developed, encapsulating nanoreactors, analyzers, and modulators, where the gate potential modulates enzyme activity and switches cascade reaction "ON" or "OFF." Such electric field-effect property enhances catalytic efficiency of enzyme by 343.4-fold and enables sensitive sarcosine assay for prostate cancer diagnoses, with a limit of detection five orders of magnitude lower than methodologies in clinical laboratory. By coupling with solid-state electronics, this work provides a perspective to construct intelligent nano-systems for precision chemistry.

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.

Towards detection of biomarkers in the eye using an aptamer-based graphene affinity nanobiosensor.

We present an approach to enable the sensitive and specific detection of biomarkers in undiluted tears in the eye using an aptamer-based graphene affinity nanosensor. The nanosensor is a graphene field-effect transistor, in which a nucleic acid aptamer and a biomolecule-permeable polyethylene glycol (PEG) nanolayer are immobilized on the graphene surface. The aptamer is capable of specifically recognize the target biomarker and induce a change in the carrier concentration of the graphene, which is measured to determine the biomarker concentration. The PEG nanolayer minimizes nonspecific adsorption of background molecules in the sample that would otherwise interfere with the biomarker detection. Experimental results show that tumor necrosis factor alpha (TNF-alpha), an inflammatory cytokine, can be sensitively and specifically detected in undiluted artificial tears with a limit of detection of 0.34 pM. This ability to detect and measure biomarkers in undiluted physiological fluids allows the nanosensor to be potentially used in applications where sample dilutions are not practical, such as wearable measurements of tear-borne biomarkers in the eye.

Ultrasensitive Graphene-Based Nanobiosensor for Rapid Detection of Hemoglobin in Undiluted Biofluids.

Detection of hemoglobin (Hb), a critical part of the biological system that is responsible for oxygen transportation, is of great significance on clinical diagnosis of various diseases. Particularly, time-efficient Hb detection under nanomole levels has drawn much attention in recent years. Herein, we present a graphene field effect transistor (GFET)-based aptameric nanobiosensor for rapid detection of Hb in undiluted biofluids including serum and urine and for the first time use polyethylenimine (PEI), a kind of comparatively low-cost polymer consisting of numerous amino groups, which can be directly linked with the anchor molecule without any pretreatment as the graphene surface passivation agent. Experimental results indicate the PEI-modified graphene aptameric nanobiosensor can respond to the Hb concentration change in a few minutes (6-8 min) with estimated detection limits of 10.6 fM in 1× PBS, 14.2 fM in undiluted serum, and 11.9 fM in undiluted urine, respectively. Further, considering the potential use of our sensor for implantable and wearable applications, we also examine the sensing performance of the sensor fabricated on an ultrathin flexible polyethylene terephthalate (PET) substrate. The Hb detection results are almost invariable even after 100 cycles of cyclic extension by 120% or 100 cycles of bending with a radius of 1 mm. Hence, our sensor holds great potential for accurate monitoring of nanomole levels of Hb in clinical applications.

Effects of Chinese wolfberry and Astragalus extract on the antioxidant capacity of Tibetan pig liver.

The objective of this study is to determine the effect of Chinese wolfberry (Lycium barbarum) and Astragalus (Astragalus membranaceus) extract (WAE) on the antioxidant capacity of Tibetan pig liver, and discussed the regulatory effect of WAE on the liver antioxidant mechanism. Twelve healthy 120-day-old Tibetan black pigs (35±2 kg) were divided randomly into two groups. The WAE group was fed a basal diet supplemented with 1% WAE for 90 days. The control group was fed the same diet, but without the WAE. We found that liver superoxide dismutase 1 (SOD1) activity (P<0.05), total antioxidative capacity (T-AOC) (P<0.05), and catalase (CAT) activity (P<0.01) significantly increased in the WAE group compared with the control group; malondialdehyde (MDA) content decreased, but this was not significant (P >0.05). Transcriptome sequencing analysis detected 106 differentially expressed genes (DEGs) related to oxidative stress. GO enrichment analysis showed these DEGs were involved in the positive regulation of reactive oxygen metabolism and biosynthesis, process regulation, and regulation of the oxidative stress response. KEGG Pathway enrichment analysis showed they were enriched in the PI3K-Akt, AMPK, Rap1, and peroxisome signaling pathways. The expression levels of key peroxisome biosynthesis genes (e.g., PEX3 and PEX11B) and key antioxidant genes (e.g., CAT and SOD1) were significantly higher in the WAE group than in the control group. The PRDX1 and PRDX5 content also was significantly higher in the WAE group. This study showed that the WAE regulated the antioxidant and anti-stress ability of Tibetan pig liver through a "peroxisome antioxidant-oxidant stress" signaling pathway.

Birds and plastic pollution: recent advances.

Plastic waste and debris have caused substantial environmental pollution globally in the past decades, and they have been accumulated in hundreds of terrestrial and aquatic avian species. Birds are susceptible and vulnerable to external environments; therefore, they could be used to estimate the negative effects of environmental pollution. In this review, we summarize the effects of macroplastics, microplastics, and plastic-derived additives and plastic-absorbed chemicals on birds. First, macroplastics and microplastics accumulate in different tissues of various aquatic and terrestrial birds, suggesting that birds could suffer from the macroplastics and microplastics-associated contaminants in the aquatic and terrestrial environments. Second, the detrimental effects of macroplastics and microplastics, and their derived additives and absorbed chemicals on the individual survival, growth and development, reproductive output, and physiology, are summarized in different birds, as well as the known toxicological mechanisms of plastics in laboratory model mammals. Finally, we identify that human commensal birds, long-life-span birds, and model bird species could be utilized to different research objectives to evaluate plastic pollution burden and toxicological effects of chronic plastic exposure.

Effects of Chinese wolfberry and astragalus extracts on growth performance, pork quality, and unsaturated fatty acid metabolism regulation in Tibetan fragrant pigs.

We studied the effects of wolfberry and astragalus extract on the growth performance, carcass traits, and meat quality of Tibetan fragrant pigs, and we want to explain the mechanism of the difference from the level of RNA Seq. Twelve healthy 120-day-old Tibetan fragrant pigs weighing 35 ± 2 kg were divided randomly into two groups, each with six pigs. The control group was fed a basal diet, and the wolfberry and astragalus extract (WAE) group was fed a basal diet +1‰ of WAE. The experimental period was 90 days. Compared with the control group, the growth performance of the WAE group was significantly improved (p < .05), pork marble score significantly improved (p < .05), vitamin E content significantly increased (p < .05), unsaturated fatty acid content significantly increased (p < .05). A total of 256 differentially expressed genes were obtained by transcriptome sequencing, among which 114 were up-regulated and 142 were down-regulated. GO analysis showed that the differentially expressed genes were related to biological functions, such as monounsaturated fatty acid biosynthesis, fatty acid metabolism, lipoprotein decomposition, and lipase activity. Pathway analysis showed that these differentially expressed genes were mainly involved in unsaturated fatty acid biosynthesis regulation, glycerin metabolism, and lipopolysaccharide regulation in fat. WAE improved Tibetan fragrant pigs growth performance. By intervening in key genes related to fatty acid metabolism, the unsaturated fatty acid contents in pork were regulated, which improved the nutritional value of the pork.

The Pre-Implantation Embryo Induces Uterine Inflammatory Reaction in Mice.

It has been well established that uterine function during the peri-implantation period is precisely regulated by ovarian estrogen and progesterone. The embryo enters the uterine cavity before implantation. However, the impact of pre-implantation embryo on uterine function is largely unknown. In the present study, we performed RNA-seq analysis of mouse uterus on day 4 morning of natural pregnancy (with embryos in the uterus) and pseudo-pregnancy (without embryos in the uterus). We found that 146 genes were upregulated, and 77 genes were downregulated by the pre-implantation embryo. Gene ontology and gene network analysis highlighted the activation of inflammatory reaction in the uterus. By examining the promoter region of differentially expressed genes, we found that NF-kappaB was a causal transcription factor. Finally, we validated 4 inflammation-related genes by quantitative RT-PCR. These 4 genes are likely the main mediators of the inflammatory reaction in the uterus triggered by the pre-implantation embryo. Our data indicated that the pre-implantation embryo causes uterine inflammatory reaction, which in turn might contribute to the establishment of uterine receptivity and embryo implantation.

A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids.

A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body.

Modulating the Linker Immobilization Density on Aptameric Graphene Field Effect Transistors Using an Electric Field.

Aptameric graphene-based field-effect transistors (A-GFETs) always employ linkers, which could immobilize on graphene through π-π stacking between contained pyrenyl groups and graphene, to anchor aptamers. Aptamer density is closely associated with the A-GFET sensitivity and determined by the linker density. Using known linker immobilization methods, the linker density is random, uncontrollable, and limited. In this work, we propose a novel linker immobilization method which can be used to effectively modulate the linker density using an electric field and further bridge the relationship between the linker density and the A-GFET sensitivity. Here, polar molecule 1-pyrenebutanoic acid succinimidyl ester (PASE) is used as a linker representative. In the electric field, PASE is arranged regularly with the electron-rich pyrenyl group forced toward graphene in the solution due to electrostatic repulsion, thereby making it possible to modulate the quantity of PASE molecules that could interact with graphene by tuning the electric field application and then realizing the regulation of the A-GFET sensitivity. Experimental results indicate that the limits of detection (LODs) of A-GFETs for detecting interleukin-6 (IL-6) and insulin can be significantly improved to be 618 and 766 fM, respectively, by applying an electric field at -0.3 V for 3 h during PASE immobilization.