Oligodendroglial connexin 47 regulates neuroinflammation upon autoimmune demyelination in a novel mouse model of multiple sclerosis.

In multiple sclerosis plaques, oligodendroglial connexin (Cx) 47 constituting main gap junction channels with astroglial Cx43 is persistently lost. As mice with Cx47 single knockout exhibit no demyelination, the roles of Cx47 remain undefined. We aimed to clarify the effects of oligodendroglia-specific Cx47 inducible conditional knockout (icKO) on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein peptide (MOG35-55) in PLP/CreERT;Cx47fl/fl mice at 14 d after tamoxifen injection. Cx47 icKO mice demonstrated exacerbation of acute and chronic relapsing EAE with more pronounced demyelination than Cx47 flox (fl)/fl littermates. CD3+ T cells more abundantly infiltrated the spinal cord in Cx47 icKO than in Cx47 fl/fl mice throughout the acute to chronic phases. CXCR3-CCR6+CD4+ and IL17+IFNγ-CD4+ helper T (Th) 17 cells isolated from spinal cord and brain tissues were significantly increased in Cx47 icKO mice compared with Cx47 fl/fl mice, while MOG35-55-specific proliferation and proinflammatory cytokine production of splenocytes were unaltered. Microarray analysis of isolated microglia revealed stronger microglial activation toward proinflammatory and injury-response phenotypes with increased expressions of chemokines that can attract Th17 cells, including Ccl2, Ccl3, Ccl4, Ccl7, and Ccl8, in Cx47 icKO mice compared with Cx47 fl/fl mice. In Cx47 icKO mice, NOS2+ and MHC class II+ microglia were more enriched immunohistochemically, and A1-specific astroglial gene expressions and astroglia immunostained for C3, a representative A1 astrocyte marker, were significantly increased at the acute phase, compared with Cx47 fl/fl mice. These findings suggest that oligodendroglia-specific Cx47 ablation induces severe inflammation upon autoimmune demyelination, underscoring a critical role for Cx47 in regulating neuroinflammation.

Brain gray matter astroglia-specific connexin 43 ablation attenuates spinal cord inflammatory demyelination.

BACKGROUND: Brain astroglia are activated preceding the onset of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We characterized the effects of brain astroglia on spinal cord inflammation, focusing on astroglial connexin (Cx)43, because we recently reported that Cx43 has a critical role in regulating neuroinflammation. METHODS: Because glutamate aspartate transporter (GLAST)+ astroglia are enriched in the brain gray matter, we generated Cx43fl/fl;GLAST-CreERT2/+ mice that were brain gray matter astroglia-specific Cx43 conditional knockouts (Cx43 icKO). EAE was induced by immunization with myelin oligodendroglia glycoprotein (MOG) 35-55 peptide 10 days after tamoxifen injection. Cx43fl/fl mice were used as controls. RESULTS: Acute and chronic EAE signs were significantly milder in Cx43 icKO mice than in controls whereas splenocyte MOG-specific responses were unaltered. Histologically, Cx43 icKO mice showed significantly less demyelination and fewer CD45+ infiltrating immunocytes, including F4/80+ macrophages, and Iba1+ microglia in the spinal cord than controls. Microarray analysis of the whole cerebellum revealed marked upregulation of anti-inflammatory A2-specific astroglia gene sets in the pre-immunized phase and decreased proinflammatory A1-specific and pan-reactive astroglial gene expression in the onset phase in Cx43 icKO mice compared with controls. Astroglia expressing C3, a representative A1 marker, were significantly decreased in the cerebrum, cerebellum, and spinal cord of Cx43 icKO mice compared with controls in the peak phase. Isolated Cx43 icKO spinal microglia showed more anti-inflammatory and less proinflammatory gene expression than control microglia in the pre-immunized phase. In particular, microglial expression of Ccl2, Ccl5, Ccl7, and Ccl8 in the pre-immunized phase and of Cxcl9 at the peak phase was lower in Cx43 icKO than in controls. Spinal microglia circularity was significantly lower in Cx43 icKO than in controls in the peak phase. Significantly lower interleukin (IL)-6, interferon-γ, and IL-10 levels were present in cerebrospinal fluid from Cx43 icKO mice in the onset phase compared with controls. CONCLUSIONS: The ablation of Cx43 in brain gray matter astroglia attenuates EAE by promoting astroglia toward an anti-inflammatory phenotype and suppressing proinflammatory activation of spinal microglia partly through depressed cerebrospinal fluid proinflammatory cytokine/chemokine levels. Brain astroglial Cx43 might be a novel therapeutic target for MS.

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking.

Chemical probes of epigenetic 'readers' of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in normal physiology and disease pathogenesis. Here we report the development of the first class of chemical probes of YEATS domains, newly identified 'readers' of histone lysine acetylation (Kac) and crotonylation (Kcr). Guided by the structural analysis of a YEATS-Kcr complex, we developed a series of peptide-based inhibitors of YEATS domains by targeting a unique π-π-π stacking interaction at the proteins' Kcr recognition site. Further structure optimization resulted in the selective inhibitors preferentially binding to individual YEATS-containing proteins including AF9 and ENL with submicromolar affinities. We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.

Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride Parkinson's disease animal model.

BACKGROUND: The first pathology observed in Parkinson's disease (PD) is 'dying back' of striatal dopaminergic (DA) terminals. Connexin (Cx)30, an astrocytic gap junction protein, is upregulated in the striatum in PD, but its roles in neurodegeneration remain elusive. We investigated Cx30 function in an acute PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to wild-type (WT) and Cx30 knockout (KO) mice. METHODS: On days 1 and 7 after MPTP administration, we evaluated changes in astrocytic Cx30, Cx43, glial fibrillary acidic protein, and ionised calcium-binding adapter molecule 1 expression by immunostaining and biochemical analysis. Loss of DA neurons was evaluated by tyrosine hydroxylase immunostaining. Gene expression was analysed using A1, A2, pan-reactive astrocyte microarray gene sets, and M1, M2, and M1/M2 mixed microglial microarray gene sets. Real-time PCR and in situ hybridisation were performed to evaluate glial cell-derived neurotrophic factor (Gdnf) and S100a10 expression. Striatal GDNF protein levels were determined by enzyme-linked immunosorbent assay. RESULTS: MPTP treatment induced upregulation of Cx30 and Cx43 levels in the striatum of WT and KO mice. DA neuron loss was accelerated in Cx30 KO compared with WT mice after MPTP administration, despite no change in the striatal concentration of methyl-4-phenylpyridinium+. Astrogliosis in the striatum of Cx30 KO mice was attenuated by MPTP, whereas microglial activation was unaffected. Microarrays of the striatum showed reduced expression of pan-reactive and A2 astrocyte genes after MPTP treatment in Cx30 KO compared with WT mice, while M1, M2, and M1/M2 mixed microglial gene expression did not change. MPTP reduced the number of striatal astrocytes co-expressing Gdnf mRNA and S100ß protein or S100a10 mRNA and S100ß protein and also reduced the level of GDNF in the striatum of Cx30 KO compared with WT mice. CONCLUSIONS: These findings indicate that Cx30 plays critical roles in astrocyte neuroprotection in an MPTP PD model.

Polyphenolic-Chemistry-Enabled, Mechanically Robust, Flame Resistant and Superhydrophobic Membrane for Separation of Mixed Surfactant-Stabilized Emulsions.

Superhydrophobic materials hold great promise in emulsion separation, but they have inherent mechanical weakness and are ineffective to separate mixed surfactant-stabilized emulsions. Herein, we combined the adhesion ability of polyphenol-Fe3+ bis-complexes with the high mechanical strength of carbon nanotubes (CNTs) to construct a mechanically robust and superhydrophobic coating on a collagen fiber membrane (CFM). We demonstrated that both CNTs and polyphenolic complexes competed with the surfactants adsorbed onto the emulsion droplets, serving as efficient demulsifiers to various mixed surfactant-stabilized emulsions. CFM has a 3D fibrous structure and a high limiting oxygen index, which provides high flux and flame resistance. The as-prepared superhydrophobic membrane can separate diverse anionic/nonionic and cationic/nonionic surfactant-stabilized micro- and nanoemulsions under gravity, with a separation efficiency and flux up to 99.999 % and 1695 L m-2 h-1 , respectively. The membranes also retained the emulsion separation ability after sandpaper abrasion. These features demonstrate a practical technology for emulsion separation.

Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

OBJECTIVE: To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. METHODS: Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. RESULTS: A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. CONCLUSIONS: Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia.

Cholesterol derivative-based liposomes for gemcitabine delivery: preparation, in vitro, and in vivo characterization.

As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112.57 ± 1.25 nm, the encapsulation efficiency was above 99%, and the drug loading efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes showed delayed drug release and long-term stability at 4 °C for up to 2 months. In vivo studies also showed the superiority of the Gem-Chol liposomes, and compared with free Gem, the Gem-Chol liposomes had longer circulation time. Moreover, an anti-tumor study in H22 and S180 tumor models showed that liposomal entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports a potential formulation of Gem for clinical application.

Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model.

BACKGROUND: Non-cell-autonomous motor neuronal death is suggested in a mutant Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) model, in which glial cells play significant roles in disease progression. Connexins (Cxs) form homotypic or heterotypic gap junctions (GJs) and allow direct intercellular communications among nervous tissue cells. The role of Cxs in motor neuron disease has never been investigated; therefore, we aimed to evaluate alterations of Cxs in mSOD1-transgenic (mSOD1-Tg) mice in comparison with their non-transgenic (non-Tg) littermates at the same ages. METHODS: We pathologically evaluated temporal changes to astrocytic Cx43/Cx30 and oligodendrocytic Cx47/Cx32 immunoreactivities at presymptomatic, disease-progressive, and end stages, relative to aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-2 (EAAT2), myelin-oligodendrocyte glycoprotein (MOG), and Nogo-A immunoreactivities, and observed neuronal loss by NeuN and neurofilament immunostaining, and microglial response by Iba-1 immunostaining. We also performed quantitative immunoblotting and real-time PCR analyses for Cxs. RESULTS: The mSOD1-Tg mice showed neuronal and axonal loss in the anterior horns of the lumbar spinal cord accompanied by increased activation of microglia compared with non-Tg mice at the disease-progressive and end stages. Expression patterns of Cxs were not different between mSOD1-Tg and non-Tg mice at the presymptomatic stage, but immunoreactivities for GFAP, Cx43, Cx30 and AQP4 were increased in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages. By contrast, Cx47 and Cx32 immunoreactivities were markedly diminished in Nogo-A-positive oligodendrocytes in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages, especially in oligodendrocytes showing SOD1 accumulation. EAAT2 immunoreactivity was also diminished in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages. Quantitative immunoblotting revealed a significant reduction in Cx47 and Cx32 protein levels in mSOD1-Tg mice at the disease-progressive and end stages. The levels of Cx47 and Cx32 mRNAs were also decreased at these stages. CONCLUSIONS: Our findings indicate that oligodendrocytic and astrocytic GJ proteins in the anterior horns of spinal cord in mSOD1-Tg mice are profoundly affected at the disease-progressive and end stages, where disruption of GJs among glial cells may exacerbate motor neuronal death.

Intertwisted superhydrophilic and superhydrophobic collagen fibers enabled anti-fouling high-performance separation of emulsion wastewater.

Oil-contaminated wastewater has been one of the most concerned environmental issues. Superwetting materials-enabled remediation of oil contamination in wastewater faces the critical challenge of fouling problems due to the formation of intercepted phase. Herein, high-performance separation of emulsions wastewater was accomplished by developing collagen fibers (CFs)-derived water-oil dual-channels that were comprised of intertwisted superhydrophilic and superhydrophobic CFs. The dual-channels relied on the superhydrophilic CFs to accomplish efficient demulsifying, which played the role as water-channel to enable fast transportation of water, while the superhydrophobic CFs served as the oil-transport channel to permit oil transportation. The mutual repellency between water-channel and oil-channel was essential to guarantee the stability of established dual-channels. The unique dual-channel separation mechanism fundamentally resolved the intercepted phase-caused fouling problem frequently engaged by the superwetting materials that provided single-channel separation capability. Long-lasting (1440 min) anti-fouling separations were achieved by the superwetting CFs-derived dual-channels with separation efficiency high up to 99.99%, and more than 4-fold of stable separation flux as compared with that of superhydrophilic CFs with single-channel separation capability. Our investigations demonstrated a novel strategy by using superwetting CFs to develop water-oil dual-channels for achieving high-performance anti-fouling separation of emulsions wastewater. ENVIRONMENTAL IMPLICATION: Industrial processes discard a large amount of emulsion wastewater, which seriously imperils the aquatic ecosystem. This work demonstrated a conceptual-new strategy to achieve effective remediation of emulsion wastewater via the water-oil dual-channels established by the intertwisted superhydrophilic and superhydrophobic collagen fibers (CFs). The superhydrophilic CFs enabled efficient demulsification of emulsions and played the role of water-channel for the rapid transportation of water, while the superhydrophobic CFs worked as oil-channel to permit the efficient transportation of oil pollutants. Consequently, the long-term (1440 min) anti-fouling high-performance separation of emulsion wastewater was achieved.

Strategies to reduce COVID-19 vaccine hesitancy among pregnant individuals: Data from a prospective survey of unvaccinated pregnant women.

OBJECTIVE: To explore strategies that could reduce coronavirus disease 2019 (COVID-19) vaccine hesitancy in pregnancy. METHODS: In 2021, the authors conducted a survey of pregnant women assessing attitudes and beliefs regarding COVID-19 vaccination. The present analysis reviewed trusted sources of information about COVID-19 vaccination that could reduce vaccine hesitancy among pregnant respondents. RESULTS: A total of 295 surveys were analyzed. Using 10-point Likert scales, intentions to accept COVID-19 vaccine were split between individuals with low (n = 126, 43%) and high (n = 141, 48%) intentions to receive the vaccine, with only a small percentage of women having midrange vaccination intentions (n = 28, 10%). When asked what would reduce their COVID-19 vaccine concerns, published data was the leading answer in both low (46.2%) and medium (35.7%) intention groups followed by personally knowing someone who got vaccinated during pregnancy (21.0% and 28.6% for low and medium groups, respectively). In contrast, an obstetrician's recommendation was the most common answer in the group with high intention to vaccinate (37.2%). Knowing someone who received the vaccine in pregnancy was the leading response for reducing concerns of COVID-19 vaccination among Black respondents. CONCLUSION: The survey identified several innovative and culturally specific approaches to address vaccine confidence and complacency and improve vaccine uptake in pregnant people.

O-GlcNAc transferase contributes to sex-specific placental deregulation in gestational diabetes.

INTRODUCTION: Gestational diabetes (GDM) is traditionally thought to emerge from placental endocrine dysregulations, but recent evidence suggests that fetal sex can also impact GDM development. Understanding the molecular mechanisms through which sex modulates placenta physiology can help identify novel molecular targets for future clinical care. Thus, we investigated the nutrient-sensing O-GlcNAc pathway as a potential mediator of sex-specific placenta dysfunction in GDM. METHODS: Expression levels of O-GlcNAc enzymes were measured in male and female (n = 9+/gender) human placentas based on the maternal diagnosis of GDM. We then simulated the observed differences in both BeWo cells and human syncytiotrophoblasts primary cells (SCT) from male and female origins (n = 6/gender). RNA sequencing and targeted qPCR were performed to characterize the subsequent changes in the placenta transcriptome related to gestational diabetes. RESULTS: O-GlcNAc transferase (OGT) expression was significantly reduced only in male placenta collected from mothers with GDM compared to healthy controls. Similar downregulation of OGT in trophoblast-like BeWo male cells demonstrated significant gene expression deregulations that overlapped with known GDM-related genes. Notably, placental growth hormone (GH) production was significantly elevated, while compensatory factors against GH-related insulin resistance were diminished. Inflammatory and immunologic factors with toxic effects on pancreatic ß cell mass were also increased, altogether leaning toward a decompensatory diabetic profile. Similar changes in hormone expression were confirmed in male human primary SCTs transfected with siOGT. However, down-regulating OGT in female primary SCTs did not impact hormone production. CONCLUSION: Our study demonstrated the significant deregulation of placental OGT levels in mothers with GDM carrying a male fetus. When simulated in vitro, such deregulation impacted hormonal production in BeWo trophoblast cells and primary SCTs purified from male placentas. Interestingly, female placentas were only modestly impacted by OGT downregulation, suggesting that the sex-specific presentation observed in gestational diabetes could be related to O-GlcNAc-mediated regulation of placental hormone production.

Water-oil dual-channels enabled exceptional anti-fouling performances for separation of emulsified oil pollutant.

Oil contamination has been an increasingly concerned environmental issue due to the large quantity of oily wastewater discharged by the industry. The extreme wettability-enabled single-channel separation strategy guarantees efficient separation of oil pollutant from wastewater. However, the ultra-high selective permeability forces the intercepted oil pollutant to form a blocking layer, which weakens the separation capability and slows the kinetics of permeable phase. As a consequence, the single-channel separation strategy fails to maintain a stable flux for a long-term separation process. Herein, we reported a brand-new water-oil dual-channels strategy for accomplishing an ultra-stable long-term separation of emulsified oil pollutant from oil-in-water nano-emulsion by engineering two drastically opposite extreme wettabilities (i.e. superhydrophilicity and superhydrophobicity) to build the water-oil dual-channels. The strategy established the superwetting transport channels to permit water and oil pollutant to permeate through their own channel. In this way, the generation of intercepted oil pollutant was prevented, which guaranteed an exceptional long-lasting (20 h) anti-fouling performance for successful achievement of an ultra-stable separation of oil contamination from oil-in-water nano-emulsion with high flux retention and high separation efficiency. Therefore, our investigations provided a new route for realizing ultra-stable long-term separation of emulsified oil pollutant from wastewater.

Exploring the binding mechanism and adverse toxic effects of degradation metabolites of pyrethroid insecticides to human serum albumin: Multi-spectroscopy, calorimetric and molecular docking approaches.

Pyrethroid insecticides (PIs), a class of structurally similar non-persistent organic pollutants, can be degraded and metabolized to more toxic, and longer half-life products. In this study, the binding interaction mechanisms between human serum albumin (HSA) and the main degradation metabolites of PIs, 3-phenoxybenzoic acid (3-PBA) and 4-fluoro-3-phenoxybenzoic acid (4-F-3-PBA), were studied by theoretical simulation and experimental verification. Steady state fluorescence spectra showed that the fluorescence quenching mechanism was static. According to the binding constant, 4-F-3-PBA (1.53 × 105 L mol-1) was bound more strongly to HSA than 3-PBA (1.42 × 105 L mol-1) in subdomain ⅡA (site I). It was found by isothermal titration calorimetry that the metabolites and HSA spontaneously combined mainly through hydrogen bond and van der Waals interaction. Ultraviolet absorption spectra and circular dichroism spectra showed that the metabolites caused slight changes in the microenvironment and conformation of HSA. The above results were proved by molecular docking. The toxicity properties of the metabolites were further analyzed by software, and 4-F-3-PBA was found to be more toxic than 3-PBA. Considering the high exposure level of these metabolites in food, the environment and human body, it is necessary to further explore the toxicity of PIs metabolites.

Structural Engineering-Enabled Joule Heating Effect Cooperated with Capillary Effect Toward Fast Spreading of Droplets for High-Flux Separation of Viscous Emulsion.

Viscous emulsions with poor fluidity and high adhesion are extremely difficult to separate. Herein, high-flux separation of viscous emulsions is realized by developing structural engineered collagen fibers (CFs)-based composite membrane that featured 3D conductive hierarchical fiber structure with the spaced carbon nanofibers (CNFs) and activated carbon (AC) serving as conductive network and competitive adsorption-based demulsifying sites, respectively. The as-designed membrane structure boosts fast spreading of emulsion droplets on membrane surface aided by the synergistic effect of joule heat in situ generated by the spaced CNFs and the capillary effect derived from CFs, which guarantees the full contact of viscous emulsions with the spaced AC for achieving ultra-efficient demulsifying. The permeation of resultant oily filtrate is accelerated by the capillary effect of hierarchically fibrous structured CFs to exhibit fast transport kinetics, therefore accomplishing high-flux separation. The structural engineered membrane achieves high-performance separation toward different viscous emulsions (55.4-123.7 mPa·s) with separation efficiency >99.9% and flux high up to 259 L m-2 h-1 . The investigations provide a novel structural engineering strategy for realizing high-performance separation of viscous emulsions.

Prospective randomized controlled study comparing low-cost LED and conventional phototherapy for treatment of neonatal hyperbilirubinemia.

Our objective was to carry out a prospective, randomized, single-blind study to evaluate whether light emitting diode (LED) phototherapy using a low-cost set of lights is as effective as conventional phototherapy in treating hyperbilirubinemia in neonates. The study included 45 pre-term neonates requiring phototherapy as per American Academy of Pediatrics guidelines; participants were randomized to receive phototherapy using LED-based lights, conventional fluorescent blue lights or conventional halogen lights. There were no statistically significant differences in the average bilirubin levels at the onset, at the maximum and at the end of treatment, nor in the duration of phototherapy treatment and the rate of decrease in bilirubin levels in the neonates receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy. (Differences were considered significant at p < 0.05). The average rate of decrease of bilirubin levels was 0.047 ± 0.037 mg dl(-1) h(-1), 0.055 ± 0.056 mg dl(-1) h(-1) and 0.057 ± 0.045 mg dl(-1) h(-1) in the groups receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy, respectively. The average duration of phototherapy treatment in the three groups was 108.8 ± 85.9 h, 92.8 ± 38.1 h, 110.4 ± 42.6 h, respectively. In this pilot study, LED phototherapy using a simple, low-cost set of lights was as effective as conventional phototherapy in the treatment of neonatal hyperbilirubinemia. LED phototherapy lights that deliver 30-40 µW cm(-2 )nm(-1) can be assembled in small quantities for

Landscaping Agricultural and Animal Husbandry Production Park Using Lightweight Deep Reinforcement Learning under Circular Symbiosis Concept.

The paper intends to optimize the landscape of the agricultural and animal husbandry (AG and AH) production park using the deep reinforcement learning (DRL) model under circular symbiosis. Therefore, after reviewing the relevant literature, decision tree evolutionary algorithm, and ensemble learning criteria, this paper studies and constructs the circular symbiotic industrial chain. Then, an experiment of landscaping the park and optimizing the production is made with full consideration of practical institutions. Finally, the numerical results show that the yield of several crops has been significantly improved after the landscape optimization by the proposed DRL model. Remarkably, the increase in rice yield is the most prominent. The yield of rice and wheat was about 12 kg before optimization and 18 kg after DRL model optimization, which has increased by 6 kg. This research has important reference value for improving the output efficiency of AG and AH products.

Loss of the Sympathetic Signal Produces Sterile Inflammation of the Prostate.

Neural innervations exert essential roles in the prostate. However, spatial distribution and regulatory function of such neural inputs are incompletely characterized. Here, we exploited the advanced whole-tissue immunolabeling and optical clearing technique to assess the 3D anatomy of autonomic innervations in the mouse and human prostate for the first time. We observed that sympathetic and parasympathetic inputs in the mouse prostate remained unaffected during castration-induced tissue regression. However, the pharmacologic destruction of sympathetic innervations in the mouse prostate led to sterile inflammation of the tissue, mimicking the disease condition of chronic non-bacterial prostatitis. Also, the genetic ablation of sympathetic inputs produced a similar inflammatory response. Furthermore, we showed that treatment of the specific ß2-adrenergic receptor agonists could effectively mitigate the prostate inflammation caused by such sympathetic loss. Together, these results have elucidated the new immunomodulatory function of the sympathetic signal via the ß2-adrenergic receptor in prostate inflammatory disease.

Impact of prior gestational diabetes on long-term type 2 diabetes complications.

AIMS: While women with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus (T2DM) and at a younger age, it is unknown whether T2DM following GDM is associated with worse clinical outcomes. This study aims to examine the impact of GDM on subsequent development of long-term complications of T2DM. METHODS: All women with T2DM from the National Health and Nutrition Examination Survey (NHANES), a nationally representative cross-sectional survey of US population, between 2007 and 2018 (n = 2494) were stratified into two groups: those with a history of GDM (n = 385) and those without (n = 2109). Rates of macrovascular and microvascular complications of T2DM were compared between the two groups using bivariate and multivariate analyses. RESULTS: Of 2494 participants with T2DM included in the analysis, 385 (15.4 %) had a history of GDM and 2109 (84.6 %) did not. A history of GDM was independently associated with increased risk of myocardial infarction (aOR 2.53, 95%Cl: 1.18-5.40) and likely coronary artery disease (aOR 2.15, 95 % Cl: 1.00-4.66). CONCLUSIONS: In this cohort, women with T2DM and a history of GDM had higher risk of macrovascular complications of myocardial infarction and coronary artery disease, compared to those with no history of gestational diabetes.

Improved CEEMDAN, GA, and SVR Model for Oil Price Forecasting.

Accurate prediction of crude oil prices (COPs) is a challenge for academia and industry. Therefore, the present research developed a new CEEMDAN-GA-SVR hybrid model to predict COPs, incorporating complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), a genetic algorithm (GA), and support vector regression machine (SVR). First, our team utilized CEEMDAN to realize the decomposition of a raw series of COPs into a group of comparatively simpler subseries. Second, SVR was utilized to predict values for every decomposed subseries separately. Owing to the intricate parametric settings of SVR, GA was employed to achieve the parametric optimisation of SVR during forecast. Then, our team assembled the forecasted values of the entire subseries as the forecasted values of the CEEMDAN-GA-SVR model. After a series of experiments and comparison of the results, we discovered that the CEEMDAN-GA-SVR model remarkably outperformed single and ensemble benchmark models, as displayed by a case study finished based on a time series of weekly Brent COPs.

Collagen fiber membrane as multi-functional support enabled rational design of ultrahigh-flux separation membrane for the remediation of oil contamination in water.

Membrane separation is a promising approach for the remediation of oil contamination in water. High-flux separation of membrane relies on the rational design of ultrathin active layer to significantly reduce mass transfer distance for achieving high separation flux, while the ultrathin active layer is usually fragile with poor mechanical strength, which has to be supported on a support. Herein, we employed collagen fiber membrane (CFM) as multi-functional support for the in-situ growth of polyacrylonitrile (PAN) layer by electrospinning to prepare the high-performance PAN/CFM composite membrane. Due to the amphiphilic nature and strong capillary effect, CFM played the role as multi-functional support to provide separation effectiveness and boosted separation flux. The PAN/CFM composite membrane enabled ultrahigh separation flux (e.g., 51751.59 L m-2 h-1 bar-1) to a variety of oil-in-water emulsion, which was one order of magnitude higher than that of commercial polyethersulfone membrane and 1.86-fold to that of cellulose acetate membrane. Furthermore, the PAN/CFM composite membrane retained high separation flux (e.g., 11046.97 L m-2 h-1 bar-1) during the 5th separation cycle, providing appreciable anti-fouling capability. Therefore, our findings provided a promising way to effectively resolve the problem of oil contamination in water.