Deficiency in Prader-Willi syndrome gene necdin leads to attenuated cardiac contractility.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by behavioral disturbances, hyperphagia, and intellectual disability. Several surveys indicate that PWS is also associated with cardiac abnormalities, possibly contributing to a high incidence of sudden death. However, the pathological mechanisms underlying cardiac dysfunction in PWS remain unclear. In this study, we found that deficiency in necdin, an intronless gene within PWS region, led to heart systolic and diastolic dysfunction in mice. Through yeast two-hybrid screening, we identified an interaction between necdin and non-muscle myosin regulatory light chain 12a/b (MYL12 A/B). We further showed that necdin stabilized MYL12 A/B via SGT1-heat shock protein 90 (HSP90) chaperone machinery. The zebrafish lacking the MYL12 A/B analog, MYL12.1, exhibited impaired heart function, while cardiac-specific overexpression of MYL12A normalized the heart dysfunction in necdin-deficient mice. Our findings revealed necdin dysfunction as a contributing factor to cardiomyopathy in PWS patients and emphasized the importance of HSP90 chaperone machinery and non-muscle myosin in heart fitness.

Characteristics of bioaerosol emissions from a municipal wastewater treatment plant: Health risk assessment and microbial composition.

Bioaerosols released from municipal wastewater treatment plants (MWWTPs) contain pathogenic microorganisms, if dispersed into the atmosphere, which pose potential health risks to humans. In this study, the concentrations and size distribution of bioaerosol, factors on the bioaerosol emission, exposure risk, and microbial composition in different treatment units of a MWWTP were investigated. The results showed that bioaerosol was released to different degrees in each treatment unit, with the concentrations of bioaerosol varied widely, ranging from 978 to 3710 CFU/m3. FG and PST were primary bioaerosol emission sources in MWWTP. COD concentration, wind speed (WS) and relative humidity (RH) significantly influenced bioaerosol concentrations. The proportion of inhalable particles (< 4.7 µm) ranged from 51.35 % to 83.33 %, and bioaerosol emitted from WWTP caused a non-carcinogenic risk to children by the exposure risk assessment (HI > 1), which need to be paid more attention. Bacterial, fungal and actinomycete aerosols were detected in each treatment unit of MWWTP. Among these bioaerosols, bacterial aerosol was dominant. Importantly, several pathogenic bacteria including Sphingobium, Brevundimonas, Romboutsia, Arcobacter, Acinetobacter, and Mycobacterium were identified within the airborne bacteria population, most of which originated from wastewater or sludge, particularly in the ambient air of AeT. Pathogenic bacteria from MWWTP should be studied further to determine their long-term behavior and possible health risks.

Soluble dietary fiber from Dendrocalamus brandisii (Munro) Kurz shoot improves liver injury by regulating gut microbial disorder in mice.

Bamboo shoot has long been regarded as a nutritious and healthy food. It is low in calorie and rich in high-quality dietary fiber (DF), making them a potential DF resource. However, the protective mechanism of soluble dietary fibers from Dendrocalamus brandisii (Munro) Kurz shoot (DS-SDF) on methionine and choline deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) is still unclear. This study was aimed to investigate the regulation of DS-SDF on gut microbiota in MCD diet-induced mice and its potential protective effect on liver injury. The NAFLD model was induced by the MCD diet for 8 weeks. Through observation of changes in liver function and gut microorganisms, it was found that DS-SDF supplementation could inhibit liver inflammation, improve liver injury, regulate the diversity of gut microorganisms, increase the abundance of beneficial bacteria and short-chain fatty acid-producing bacteria, and reverse the gut disorders induced by the MCD diet in mice. This study showed that DS-SDF supplementation could treat NAFLD by regulating gut microbiota composition, improving liver function, and inhibiting the inflammatory response. It might broaden the idea of high-value utilization of DS-SDF.

Multi-dimension analysis of volatile sulfur compound emissions from an urban wastewater treatment plant.

Long-term monitoring of volatile sulfur compounds (VSCs) released at the water-air interface from different treatment units of an anaerobic/oxic (A/O) wastewater treatment plant (WWTP) was carried out to assess the temporal and spatial emission characteristics of VSCs, to explore relationships between wastewater quality and VSC release. The VSC from non-aerated and aerated units were collected using dynamic and static chambers, respectively, and determined using gas chromatography. The VSC emission fluxes diminished in the order of primary sedimentation tank (PST) > anaerobic areas (ANA) > oxic section 1 (OX1). VSCs were not detected in the oxic section 2 (OX2), the oxic areas section 3 (OX3), and the final setting basin (FSB). Release capacities of VSCs descended in the order of summer > fall > spring > winter, with July, August, and September being the months with the highest VSC release capacities. VSC emission fluxes correlated well with wastewater temperatures, sulfate concentrations, and COD. VSC emission flux empirical equations based on wastewater temperature, sulfate concentrations, and COD were established. Based on the established VSC emission empirical equation, a control strategy to reduce the operating costs of deodorization facilities was proposed. This strategy is economically efficient and reduces the consumption of electrical energy.

Effects of ultrasonic assisted high-temperature cooking method on the physicochemical structure characteristics and in vitro antioxidant capacities of dietary fiber from Dendrocalamus brandisii Munro shoots.

In this study, the ultrasonic assisted high-temperature cooking extraction method of soluble dietary fiber from bamboo shoots was optimized by response surface methodology, and the effects of ultrasonic assisted high-temperature cooking extraction on the structural characteristics, physicochemical properties and antioxidant activity of soluble dietary fiber (SDF) from bamboo shoots were evaluated. The yield of modified UH-SDF1 was significantly higher than that of untreated D-SDF2. FTIR and XRD confirmed that UH-SDF had more hydrophilic groups and higher crystallinity (28.73 %), resulting in better thermal stability. SEM observation showed that UH-SDF exhibited a more loose microstructure, and the particle size of UH-SDF (601.52 µm) was significantly smaller than that of D-SDF (242.59 µm), so UH-SDF had a larger specific surface area. In addition, UH-SDF has stronger water holding capacity, water swelling capacity and oil holding capacity than D-SDF. The DPPH radical and hydroxyl radical scavenging rates of UH-SDF were 8.91 % and 7.49 % higher than those of D-SDF. In addition, the reducing ability of UH-SDF was higher than that of D-SDF, which had better antioxidant activity. In summary, UH-SDF has the potential to be developed as an anti-inflammatory functional food.

Awakening from anesthesia switches cortical wave modes.

Spontaneous cortical activity exhibits diverse spatiotemporal dynamics across brain states, but the organizational principles during state transitions remain unclear. In a recent study combining cortex-wide voltage imaging and neural modeling, Liang and colleagues revealed that global-local competition and long-range connections underlie the emergence of complex cortical wave patterns during awakening from anesthesia.

Cortical regulation of two-stage rapid eye movement sleep.

Rapid eye movement (REM) sleep is a sleep state characterized by skeletal muscle paralysis and cerebral cortical activation. Yet, global cortical dynamics and their role in regulating REM sleep remain unclear. Here we show that in mice, REM sleep is accompanied by highly patterned cortical activity waves, with the retrosplenial cortex (RSC) as a major initiation site. Two-photon imaging of layer 2/3 pyramidal neurons of the RSC revealed two distinct patterns of population activities during REM sleep. These activities encoded two sequential REM sleep substages, characterized by contrasting facial movement and autonomic activity and by distinguishable electroencephalogram theta oscillations. Closed-loop optogenetic inactivation of RSC during REM sleep altered cortical activity dynamics and shortened REM sleep duration via inhibition of the REM substage transition. These results highlight an important role for the RSC in dictating cortical dynamics and regulating REM sleep progression.

Comparison of physicochemical and in vitro hypoglycemic activity of bamboo shoot dietary fibers from different regions of Yunnan.

In this study, the physicochemical properties, thermal characteristics, and in vitro hypoglycemic activity of dietary fibers extracted from four bamboo shoots were characterized and compared. The results showed that Dendrocalamus brandisii Munro (C-BSDF) had the highest dietary fiber content (6.1%) and the smallest particle size (222.21 µm). SEM observations found that C-BSDF exhibited a loose and porous microstructure, while FTIR and XRD confirmed that C-BSDF had a higher degree of decomposition of insoluble dietary fiber components and the highest crystallinity, resulting in a better microstructure. Furthermore, C-BSDF exhibited excellent physiochemical properties with the highest water hold capacity, water swelling capacity, and preferable oil holding capacity. Thermal analysis showed that C-BSDF had the lowest mass loss (64.25%) and the highest denaturation temperature (114.03°C). The hypoglycemic activity of dietary fibers from bamboo shoots were examined in vitro and followed this order of activity: C-BSDF>D-BSDF>A-BSDF>B-BSDF. The inhibition ratios of GAC, GDRI and α-amylase activity of C-BSDF were 21.57 mmol/g, 24.1, and 23.34%, respectively. In short, C-BSDF display excellent physicochemical and functional properties due to its high soluble dietary fiber content, small particle size with a high specific surface area, and loose microstructure. Thus, D. brandisii Munro can be considered a promising new source of dietary fiber for hypoglycemic health products.

Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery.

Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin-proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.

Hyperactive Akt-mTOR pathway as a therapeutic target for pain hypersensitivity in Cntnap2-deficient mice.

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily that is involved in many neurological diseases, such as autism and pain hypersensitivity. We recently found that Cntnap2-/- mice showed elevated Akt-mTOR activity in the brain, and suppression of the Akt-mTOR pathway rescued the social deficit in Cntnap2-/- mice. In this study, we found that the dorsal root ganglion (DRG) from Cntnap2-/- mice also showed hyperactive Akt-mTOR signaling. Treatment with the Akt inhibitor LY94002 or the mTOR inhibitor rapamycin attenuated pain-related hypersensitivity to noxious mechanical stimuli, heat, and inflammatory substances. Further, suppression of mTOR signaling by rapamycin decreased DRG neuronal hyperexcitability. We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2-/- mice. Our results thus identified hyperactive Akt-mTOR signaling pathway as a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2.