Design, synthesis, and evaluation of pirfenidone-NSAIDs conjugates for the treatment of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal, chronic and progressive lung disease that threaten public health like many cancers. In this study, targeting the significant driving factor, inflammatory response, of the IPF, several conjugates of pirfenidone (PFD) with non-steroidal anti-inflammatory drugs (NSAIDs), along with their derivatives, were designed and synthesized to enhance the anti-IPF potency of PFD. Among these compounds, the (S)-ibuprofen-PFD conjugate 5b exhibited the most potent anti-proliferation activity against NIH3T3 cells, demonstrating up to a 343-fold improvement compared to PFD (IC50 = 0.04 mM vs IC50 = 13.72 mM). Notably, 5b exhibited superior activity in inhibiting the migration of macrophages induced by TGF-ß compared to PFD. Additionally, 5b demonstrated significant suppression of TGF-ß-induced migration of NIH3T3 cells and induction of apoptosis in NIH3T3 cells. Mechanistic studies revealed that 5b reduced the expression of collagen I and α-SMA by inhibiting the TGF-ß/SMAD3 pathway. In a bleomycin-induced pulmonary fibrosis model, treatment with 5b (40 mg/kg/day, orally) exhibited a more pronounced effect on reducing the degree of histopathological changes in lung tissue and alleviating collagen deposition compared to PFD (100 mg/kg/day, orally). Moreover, 5b could block the expression of collagen I, α-SMA, fibronectin, and pro-inflammatory factors (IL-6, IFN-γ, and TNF-α) compared to PFD, while demonstrating low toxicity in vivo. These preliminary results indicated that the hybridization of PFD with NSAIDs represented an effective modification approach to improve the anti-IPF potency of PFD. Consequently, 5b emerged as a promising candidate for the further development of new anti-IPF agents.

A Bacterial Responsive Microneedle Dressing with Hydrogel Backing Layer for Chronic Wound Treatment.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Inhaled pulmonary surfactant biomimetic liposomes for reversing idiopathic pulmonary fibrosis through synergistic therapeutic strategy.

Idiopathic pulmonary fibrosis (IPF) stands as a highly heterogeneous and deadly lung disease, yet the available treatment options remain limited. Combining myofibroblast inhibition with ROS modulation in damaged AECs offers a comprehensive strategy to halt IPF progression, but delivering drugs separately to these cell types is challenging. Inspired by the successful application of pulmonary surfactant (PS) replacement therapy in lung disease treatment, we have developed PS nano-biomimetic liposomes (PSBs) to utilize its natural transport pathway for targeting AECs while reducing lung tissue clearance. In this collaborative pulmonary drug delivery system, PSBs composed of DPPC/POPG/DPPG/CHO (20:9:5:4) were formulated for inhalation. These PSBs loaded with ROS-scavenger astaxanthin (AST) and anti-fibrosis drug pirfenidone (PFD) were aerosolized for precise quantification and mimicking patient inhalation. Through aerosol inhalation, the lipid membrane of PSBs gradually fused with natural PS, enabling AST delivery to AECs by hitchhiking with PS circulation. Simultaneously, PFD was released within the PS barrier, effectively penetrating lung tissue to exert therapeutic effects. In vivo results have shown that PSBs offer numerous therapeutic advantages in mice with IPF, particularly in terms of lung function recovery. This approach addresses the challenges of drug delivery to specific lung cells and offers potential benefits for IPF patients.

A Study on the Applicability of Aromatic Parameters in the Maturity Evaluation of Lacustrine Source Rocks and Oils Based on Pyrolysis Simulation Experiments.

Aromatic maturity parameters were evaluated via closed-system pyrolysis experiments using a Mesozoic lacustrine source rock from the Yingen-Ejinaqi Basin, thereby ensuring a uniform source. Pulverized rock aliquots (200 mg) were reacted with water at temperatures ranging from 250 to 550 °C at 5 °C/min, and the aromatic fractions of expelled oil and extracts of the solid residue were analyzed by GC-MS. The experiments showed that the relative abundance of aromatic hydrocarbons in the oil and extractable organic matter (EOM) of source rock had different evolutionary characteristics. With the increase in the thermal evolution degree, the relative abundance of aromatic hydrocarbons in the EOM showed the characteristics of ″increased early (Ro < 0.80), unchanged middle (Ro = 0.80-2.00%), decreased lately (Ro > 2.00%)″. While the relative abundance of aromatic hydrocarbons in the expelled oils continuously increased, as the Ro values increased from 0.62 to 2.39%, the relative abundance of aromatic hydrocarbons gradually increased from 8 to 46%. With increased maturity, the relative abundance of 1-3-ring aromatic hydrocarbons continuously decreased, as observed in the phenanthrene homologs. Meanwhile, the relative abundance of 4+-ring aromatic hydrocarbons continuously increased, as seen in chrysene homologs. It was suggested that the effects of maturity on the composition of aromatic hydrocarbons might not be sufficiently obvious. The effective application range of the alkylnaphthalene-related maturity parameters (2-/1-methylnaphthalenes, (2,6- + 2,7-)/1,5-dimethylnaphthalenes, 2,3,6-/(1,4,6- + 1,3,5-) trimethylnaphthalenes, and (2,3,6- + 1,3,7-)/(1,4,6- + 1,3,5- + 1,3,6-) trimethylnaphthalenes) and the alkyldibenzothiophene maturity parameters (4-/1-methyldibenzothiophenes, 4,6-/(1,4- + 1,6-) dimethyldibenzothiophenes, and (2,6- + 3,6-)/(1,4- + 1,6-) dimethyldibenzothiophenes) was 0.84-2.06% Ro. The alkylphenanthrene-related maturity parameters had a wide application range for lacustrine source rocks with an Ro < 2.06%. These parameters included 1.5 × (2- + 3-)/(phenanthrene +1- + 9-) methylphenanthrenes, 3 × 2-/(phenanthrene + 1- + 9-) methylphenanthrenes, (2- + 3-)/(1- + 9-) methylphenanthrenes, 2-/1-methylphenanthrenes, (3- + 2-)/(1- + 2- + 3- + 9-) methylphenanthrenes, 2-/(1- + 2- + 3- + 9-) methylphenanthrenes, and 2,7-/1,8-dimethylphenanthrenes. In addition, the effective applicable range of the methylnaphthalene-related maturity parameter 3-/1-methylchrysenes was an Ro value less than 1.79%. The results clarified the validity scope of some aromatics' maturity parameters and provided a theoretical basis for the scientific application of these parameters.

Comprehensive insight into adsorption of chlortetracycline hydrochloride by room-temperature synthesized water-stable Zr-based metal-organic gel/sodium alginate beads.

Chlortetracycline hydrochloride (CTC) is one of the prevailing antibiotic pollutants that harm both environmental ecosystem and human health. Herein, Zr-based metal-organic gels (Zr-MOGs) with lower-coordinated active sites and hierarchically porous structures are fabricated via a facile straightforward room-temperature strategy for CTC treatment. More importantly, we incorporated the powder Zr-MOGs into low-cost sodium alginate (SA) matrix to achieve shaped Zr-based metal-organic gel/SA beads for enhancing the adsorption ability and ameliorating the recyclability. The Langmuir maximum adsorption capacities of Zr-MOGs and Zr-MOG/SA beads could reach 143.9 mg/g and 246.9 mg/g, respectively. What's more, in the manual syringe unit and continuous bead column experiments, Zr-MOG/SA beads could achieve an eluted CTC removal ratio as high as 96.3% and 95.5% in the river water sample, respectively. On top of that, the adsorption mechanisms were put forward as a combination of pore filling, electrostatic interaction, hydrophilic-lipophilic balance, coordination, π-π interaction as well as hydrogen bonding interaction. This study outlines a workable strategy for the facile preparation of candidate adsorbents for wastewater treatment.

Complement system in Anti-CD20 mAb therapy for cancer: A mini-review.

The complement system is an important part of innate immunity. Through complement-dependent cytotoxicity (CDC), it plays an important role in the clearance of invading pathogens but also cancerous host cells. Therapy with anti-CD20 monoclonal antibodies (mAbs), for example, rituximab and ofatumumab, is a well-established treatment for lymphoid malignancies, and CDC is one of the main mechanisms underlying their anti-cancer activity. However, there are still some issues with the clinical application of anti-CD20 antibodies. On the one hand, anti-CD20 can cause some clinical side effects; on the other hand, anti-CD20 has low potency in some patients, and increasing the dosage does not enhance its effectiveness in these patients. Previous studies have reported that a gain-of-function in a certain complement component can boost the cytolytic activity of anti-CD20 mAbs. Through reviewing the literature on complement system control and anti-CD20 mAbs, this article aims to provide a thorough understanding of the potential of targeting complement components in lymphoma therapy.

Obstacle-induced giant jammed aggregation of active semiflexible filaments.

Filaments driven by bound motor proteins and chains of self-propelled colloidal particles are a typical example of active polymers (APs). Due to deformability, APs exhibit very rich dynamic behaviors and collective assembling structures. Here, we are concerned with a basic question: how APs behave near a single obstacle? We find that, in the presence of a big single obstacle, the assembly of APs becomes a two-state system, i.e. APs either gather nearly completely together into a giant jammed aggregate (GJA) on the surface of the obstacle or distribute freely in space. No partial aggregation is observed. Such a complete aggregation/collection is unexpected since it happens on a smooth convex surface instead of, e.g., a concave wedge. We find that the formation of a GJA experiences a process of nucleation and the curves of the transition between the GJA and the non-aggregate state form hysteresis-like loops. Statistical analysis of massive data on the growing time, chirality and angular velocity of both the GJAs and the corresponding nuclei shows the strong random nature of the phenomenon. Our results provide new insights into the behavior of APs in contact with porous media and also a reference for the design and application of polymeric active materials.

Psychological experience of inpatients with acute pancreatitis: a qualitative study.

OBJECTIVE: This study aimed to better understand the psychological experiences of inpatients with acute pancreatitis (AP). DESIGN: We used a qualitative descriptive study design to capture patients with AP's thoughts, feelings and behavioural responses. SETTING: We conducted this study in the gastroenterology departments of two tertiary hospitals in Eastern China. PARTICIPANTS: We used a convenience sampling approach to recruit 28 inpatients with AP from 1 August 2020 to 25 December 2020. The interviews were audio-recorded and transcribed verbatim. We employed an adapted version of Colaizzi's qualitative analysis approach to examine the data. RESULTS: We extracted three themes and eight subthemes regarding the participants' psychological experiences: (1) feeling that their disease is unpredictable (the inability to recognise the disease, uncertainty about the illness and fear of progression or recurrence); (2) various kinds of stress and support (feeling different degrees of stress, perceiving social support, seeking and craving social support); and (3) developing self-adaptability in the disease process (treating one's illness negatively or positively). CONCLUSIONS: Cognitive and emotional responses vary in patients with AP during hospitalisation. Moreover, patients with distinct conditions demonstrate significant differences in their responses and coping mechanisms. Healthcare providers need to mobilise social support and formulate comprehensive intervention strategies according to patients' individual characteristics.

A multi-modal open dataset for mental-disorder analysis.

According to the WHO, the number of mental disorder patients, especially depression patients, has overgrown and become a leading contributor to the global burden of disease. With the rising of tools such as artificial intelligence, using physiological data to explore new possible physiological indicators of mental disorder and creating new applications for mental disorder diagnosis has become a new research hot topic. We present a multi-modal open dataset for mental-disorder analysis. The dataset includes EEG and recordings of spoken language data from clinically depressed patients and matching normal controls, who were carefully diagnosed and selected by professional psychiatrists in hospitals. The EEG dataset includes data collected using a traditional 128-electrodes mounted elastic cap and a wearable 3-electrode EEG collector for pervasive computing applications. The 128-electrodes EEG signals of 53 participants were recorded as both in resting state and while doing the Dot probe tasks; the 3-electrode EEG signals of 55 participants were recorded in resting-state; the audio data of 52 participants were recorded during interviewing, reading, and picture description.

Impact of Fatty Pancreas on Postoperative Pancreatic Fistulae: A Meta-Analysis.

BACKGROUND: Soft pancreas is widely recognized as an important risk factor for the development of postoperative pancreatic fistula (POPF). Although fatty pancreas (FP) has not been formally defined as a cause of pancreatic fistula, existing research has shown that it can increase the incidence of POPF by increasing pancreatic tenderness; therefore, it may be a potential risk factor. This study aimed to discern whether FP was associated with POPF. METHOD: Two reviewers independently performed literature searches from five electronic databases. According to the established inclusion criteria, we extracted necessary data from the studies that met the criteria for further analysis. We pooled the odds ratios (ORs) from individual studies using a random-effects model to investigate the associations between POPF and the prognosis of FP. RESULT: A total of 11 studies involving 2484 individuals were included. The pooled prevalence of POPF was 18% (95% CI: 12-24%). Body mass index (BMI) was associated with a significantly increased risk of POPF (OR=3.55; 95% CI: 1.83, 6.86; P=0.0002; I²=0). FP was obviously associated with the occurrence of POPF (OR=3.75; 95% CI: 1.64, 8.58; P=0.002; I²=78). CONCLUSION: FP is closely associated with the development of POPF, and the early identification of these high-risk patients can help to reduce the incidence of POPF. SYSTEMATIC REVIEW REGISTRATION: The Registration URL link is (https://www.crd.york.ac.uk/PROSPERO/). The ID is "CRD42021265141".

25(OH)-Vitamin D alleviates neonatal infectious pneumonia via regulating TGFß-mediated nuclear translocation mechanism of YAP/TAZ.

Neonatal infectious pneumonia (NIP) is a common infectious disease that develops in the neonatal period. The purpose of our study was to explore the potential roles of 25(OH)-Vitamin D (25-OH-VD) and its anti-inflammatory mechanism in NIP. The results showed that serum 25-OH-VD level was negatively correlated with the severity of NIP, whereas Spearman's correlation analysis showed a significant positive correlation between the severity of NIP and the levels of pneumonia markers procalcitonin (PCT) and interleukin-6 (IL-6). The expression of vitamin D receptor (VDR) was down-regulated, while the transforming growth factor ß (TGFß), nuclear YAP, and TAZ were up-regulated in the peripheral blood mononuclear cells (PBMCs) of neonates with severe pneumonia. Neonates with 25-OH-VD deficiency were associated with an increased risk of NIP. In BEAS-2B cells, down-regulation of nuclear YAP and TAZ was found in the lipopolysaccharide (LPS) + VD group relative to the LPS-induced group. Additionally, positive rate of nuclear YAP, as detected by immunocytochemistry (ICC), and the nuclear translocation of nuclear YAP/TAZ by IFA in the LPS+VD group showed an intermediate level between that of the control and LPS-induced groups. Furthermore, the expressions of VDR and CYP27B1 were significantly increased in the LPS+VD group as compared to those in the LPS-induced group. The anti-inflammatory mechanism in NIP was achieved due to the 25-OH-VD mediating TGFß/YAP/TAZ pathway, which suggested that using 25-OH-VD might be a potential strategy for NIP treatment.

Syringin Prevents Aß25-35-Induced Neurotoxicity in SK-N-SH and SK-N-BE Cells by Modulating miR-124-3p/BID Pathway.

Alzheimer's disease (AD) is a neurodegenerative disorder disease, disturbing people's normal life. Syringin was mentioned to antagonize Amyloid-ß (Aß)-induced neurotoxicity. However, the action mechanism is still not fully elucidated. This study aimed to explore a molecular mechanism of syringin in defending Aß-induced neurotoxicity. SK-N-SH and SK-N-BE cells were treated with amyloid ß-protein fragment 25-35 (Aß25-35) to induce cell neurotoxicity. The injury effects were distinguished by assessing cell viability and cell apoptosis using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of Cleaved-caspase3 (Cleaved-casp3), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and BH3 interacting domain death agonist (BID) at the protein level was determined by western blot. The expression of miR-124-3p and BID was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-124-3p and BID was predicted by the online database starBase and confirmed by dual-luciferase reporter assay plus RNA pull-down assay. Aß25-35 treatment inhibited cell viability and induced cell apoptosis, while the addition of syringin recovered cell viability and suppressed cell apoptosis. MiR-124-3p was significantly downregulated in Aß25-35-treated SK-N-SH and SK-N-BE cells, and BID was upregulated. Nevertheless, the addition of syringin reversed their expression. BID was a target of miR-124-3p, and its downregulation partly prevented Aß25-35-induced injuries. Syringin protected against Aß25-35-induced neurotoxicity by enhancing miR-124-3p expression and weakening BID expression, and syringin strengthened the expression of miR-124-3p to diminish BID level. Syringin ameliorated Aß25-35-induced neurotoxicity in SK-N-SH and SK-N-BE cells by regulating miR-124-3p/BID pathway, which could be a novel theoretical basis for syringin to treat AD.

Downregulation of lncRNA XIST Represses Tumor Growth and Boosts Radiosensitivity of Neuroblastoma via Modulation of the miR-375/L1CAM Axis.

Neuroblastoma (NB) is a heterogeneous tumor that is common in infants and young children. Long non-coding RNA X-inactive specific transcript (XIST) is implicated in NB advancement. Nevertheless, the role and regulatory mechanism by which XIST in NB are not fully elucidated. Expression levels of XIST, microRNA-375-5p (miR-375), and L1 cell adhesion molecular (L1CAM) were examined through quantitative real-time polymerase chain reaction (qRT-PCR). The cell cycle progression, proliferation, and colony formation of NB cells were determined with flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), or cell colony formation assays. Cell apoptotic rate was detected with flow cytometry assay. The relationship between XIST or L1CAM and miR-375 was verified via dual-luciferase reporter assay. The level of L1CAM protein was examined through western blotting. The role of XIST in vivo was confirmed through xenograft assay. XIST and L1CAM were upregulated while miR-375 was downregulated in NB tissues and cells. XIST depletion repressed tumor growth in vivo and elevated radiosensitivity, arrested cell cycle progression, and impeded proliferation of NB cells in vitro. Mechanistically, XIST modulated L1CAM expression through competitively binding to miR-375. Furthermore, miR-375 inhibitor recovered XIST inhibition-mediated effects on the radiosensitivity and malignant behaviors of NB cells. Also, L1CAM overexpression reversed the effects of miR-375 enhancement on the cell cycle progression, proliferation, and radiosensitivity of NB cells. XIST downregulation repressed tumor growth and boosted radiosensitivity of NB via modulating the miR-375/L1CAM axis, indicating that XIST was a promising target for NB treatment.

lncRNA SNHG1 Knockdown Alleviates Amyloid-ß-Induced Neuronal Injury by Regulating ZNF217 via Sponging miR-361-3p in Alzheimer's Disease.

BACKGROUND: Long noncoding RNAs have been proven to play an important role in the progression of Alzheimer's disease (AD). However, the function of small nucleolar RNA host gene 1 (SNHG1) in AD progression remains to be studied. OBJECTIVE: To explore the role of SNHG1 in AD progression and clarify its potential mechanism. METHODS: Amyloid ß-protein (Aß) was used to construct an AD cell model in vitro. The expression levels of SNHG1 and miR-361-3p were determined by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit 8 assay and flow cytometry. The levels of apoptosis-related proteins and zinc finger gene 217 (ZNF217) protein were evaluated by western blot analysis. Additionally, the contents of inflammatory cytokines and oxidative stress markers were tested by enzyme-linked immunosorbent assay. Furthermore, dual-luciferase reporter and RNA immunoprecipitation assays were used to verify the interaction between miR-361-3p and SNHG1 or ZNF217. RESULTS: Aß could induce cell injury, while resveratrol could reverse this effect. SNHG1 expression was positively regulated by Aß and negatively regulated by resveratrol. SNHG1 knockdown could reverse the promotion effect of Aß on cell injury. Moreover, SNHG1 sponged miR-361-3p, and miR-361-3p targeted ZNF217. Additionally, miR-361-3p overexpression reversed the promotion effect of SNHG1 overexpression on cell injury, and ZNF217 silencing also reversed the promotion effect of miR-361-3p inhibitor on cell injury. CONCLUSION: SNHG1 promoted cell injury by regulating the miR-361-3p/ZNF217 axis, which might provide a theoretical basis for molecular therapy of AD.

Berberine attenuates Aß42-induced neuronal damage through regulating circHDAC9/miR-142-5p axis in human neuronal cells.

BACKGROUND: Berberine plays a neuroprotective role in neurodegenerative diseases, including Alzheimer's disease (AD). Circular RNAs (circRNAs) function as crucial players in AD pathogenesis. In the current work, we aimed to investigate whether circRNA histone deacetylase 9 (circHDAC9) was involved in the regulation of berberine in AD. METHODS: Cell viability and apoptosis were determined by the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assess caspase-3 activity and the production of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α). The levels of circHDAC9 and miR-142-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Subcellular fractionation assays were performed to evaluate the localization of circHDAC9. The direct interaction between circHDAC9 and miR-142-5p was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. RESULTS: Our data indicated that circHDAC9 was indeed a circular transcript and mainly localized in the cytoplasm. 42-residue ß-amyloid (Aß42) triggered a significant down-regulation in circHDAC9 and a striking up-regulation in miR-142-5p in human neuronal (HN) cells. Berberine relieved Aß42-induced HN cell neurotoxicity. Moreover, berberine resulted in increased circHDAC9 expression and decreased miR-142-5p level in Aß42-treated HN cells. Berberine alleviated Aß42-induced neuronal damage in HN cells by up-regulating circHDAC9. Furthermore, circHDAC9 acted as a molecular sponge of miR-142-5p. CircHDAC9 overexpression alleviated Aß42-induced HN cell neurotoxicity via miR-142-5p. CONCLUSION: Our current study suggested that berberine protected HN cell from Aß42-induced neuronal damage at least partly through regulating the circHDAC9/miR-142-5p axis, highlighting novel evidence for the neuroprotective effect of berberine in AD.

Construction of magnetic NiO/C nanosheets derived from coordination polymers for extraordinary adsorption of dyes.

Herein, a facial stratagem for the large-scale synthesis of NiO/C nanosheets used as magnetic adsorbents is proposed by using nanoscale coordination polymers (nanoCPs) as precursors. The NiO nanoparticles (NPs) scattered on the NiO/C nanosheets have an untrasmall size (~3 nm) as well as uniform dispersion, since the Ni2+ ions are preassembled into the nanoCPs precursors by coordination bonds and transformed to NiO NPs in situ under the restriction of carbon layers. Thanks to the small size and spatially uniform distribution of NiO NPs, fully exposed carbon matrix containing part of graphene structures, and the high specific surface area of the special nanosheet structure, the magnetic NiO/C nanosheets have an a great breakthrough in the adsorption performance toward Congo Red (CR) among many reported NiO-based materials. The maximum adsorption capacity for CR is up to 2000 mg/g, and the adsorption kinetics and thermodynamics are also systematically studied. Moreover, the NiO/C nanosheets can be separated from water and reused simply by an external magnetic field. The NiO/C nanosheets with low cost and extraordinary adsorption ability have great potential in water pollution treatment area.

miR-16-5p and miR-19b-3p prevent amyloid ß-induced injury by targeting BACE1 in SH-SY5Y cells.

PURPOSE: Alzheimer's disease is the most common neurodegenerative disease, characterized by accumulation of amyloid ß peptides. MicroRNAs have been identified as significant regulators and therapeutic targets of Alzheimer's disease. However, the roles of miR-16-5p and miR-19b-3p and their mechanisms in Alzheimer's disease progression remain largely unknown. MATERIALS AND METHODS: Amyloid ß-treated SH-SY5Y cells were used to study Alzheimer's disease progression in vitro. Transfection was conducted into SH-SY5Y cells using Lipofectamine 2000. The expression levels of miR-16-5p, miR-19b-3p and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) were measured by quantitative real-time PCR or western blot, respectively. Cell viability and apoptosis were detected in amyloid ß-treated SH-SY5Y cells by MTT or flow cytometry, respectively. The interaction between BACE1 and miR-16-5p or miR-19b-3p was explored by luciferase reporter and RNA immunoprecipitation analyses. RESULTS: The expression levels of miR-16-5p and miR-19b-3p were reduced but BACE1 protein expression was enhanced in SH-SY5Y cells after treatment of amyloid ß. Overexpression of miR-16-5p or miR-19b-3p attenuated amyloid ß-induced viability inhibition and apoptosis promotion in SH-SY5Y cells, while their knockdown exacerbated amyloid ß-induced injury. BACE1 was confirmed as a target of miR-16-5p and miR-19b-3p and its overexpression aggravated amyloid ß-induced loss of viability and production of apoptosis, while its depletion caused an opposite effect. Moreover, upregulation of BACE1 alleviated the regulatory effects of miR-16-5p and miR-19b-3p on amyloid ß-induced injury. CONCLUSION: MiR-16-5p and miR-19b-3p relieved amyloid ß-induced injury by targeting BACE1 in SH-SY5Y cells, indicating miR-16-5p and miR-19b-3p as protective agents for treatment of Alzheimer's disease.

[Risk factors for elevated serum total bile acid in preterm infants].

OBJECTIVE: To study the risk factors for elevated serum total bile acid (TBA) in preterm infants. METHODS: A retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 µmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA. RESULTS: The univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants. CONCLUSIONS: Low birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.

SWELL1 is a glucose sensor regulating ß-cell excitability and systemic glycaemia.

Insulin secretion is initiated by activation of voltage-gated Ca2+ channels (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the ß-cell plasma membrane. The firing of VGCC requires ß-cell membrane depolarization, which is regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here, we show that SWELL1 mediates a swell-activated, depolarizing chloride current (ICl,SWELL) in both murine and human ß-cells. Hypotonic and glucose-stimulated ß-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to membrane depolarization and activation of VGCC-dependent intracellular calcium signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs glucose-stimulated insulin secretion. Tamoxifen-inducible ß-cell-targeted Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired glucose-stimulated insulin secretion and glucose tolerance; and this is further exacerbated in mild obesity. Our results reveal that ß-cell SWELL1 modulates insulin secretion and systemic glycaemia by linking glucose-mediated ß-cell swelling to membrane depolarization and activation of VGCC-triggered calcium signaling.