Polarity-Mediated Antisolvent Control Enables Efficient Lanthanide-Based near-Infrared Perovskite LEDs.

Alloying lanthanide ions (Yb3+) into perovskite quantum dots (Yb3+:CsPb(Cl1-xBrx)3) is an effective method to achieve efficient near-infrared (NIR) luminescence (>950 nm). Increasing the Yb3+ alloying ratio in the perovskite matrix enhances the luminescence intensity of Yb3+ emission at 990 nm. However, high Yb3+ alloying (>15%) results in vacancy-induced inferior material stability. In this work, we developed a polarity-mediated antisolvent manipulation strategy to resolve the incompatibility between a high Yb3+ alloying ratio and inferior stability of Yb3+:CsPb(Cl1-xBrx)3. Precise control of solution polarity enables increased uniformity of the perovskite matrix with fewer trap densities. Employing this strategy, we obtain Yb3+:CsPb(Cl1-xBrx)3 with the highest Yb3+ alloying ratio of 30.2% and a 2-fold higher electroluminescence intensity at 990 nm. We lever the engineered Yb3+:CsPb(Cl1-xBrx)3 to fabricate NIR-LEDs, achieving a peak external quantum efficiency (EQE) of 8.5% at 990 nm: this represents the highest among perovskite NIR-LEDs with an emission wavelength above 950 nm.

Modulatory effects of dietary saturated fatty acids on platelet mitochondrial function following short-term exposure to ambient Particulate Matter (PM2.5).

Exposure to ambient fine particulate matter (PM2.5) was found to produce vascular injury, possibly by activating platelets within days after exposure. The aim of this study was to investigate the modulatory effects of dietary saturated fatty acids on platelet mitochondrial respiratory parameters following short-term inhalational exposure to PM2.5. A total of 22 healthy male volunteers were recruited from the Research Triangle area of North Carolina. Platelets were isolated from fresh whole blood samples and mitochondrial respiratory parameters were measured using an extracellular flux analyzer. Intake of saturated fat was averaged from multiple 24-hr dietary recalls. Daily ambient PM2.5 concentrations were obtained from ambient air quality monitoring stations. Correlation and ANOVA were used in data analyses, along with the pick-a-point method and the Johnson-Neyman technique for probing moderation. After controlling for age and omega-3 index, the intake of dietary saturated fatty acids after reaching 9.3% or higher of the total caloric intake significantly moderated the associations between PM2.5 exposure and several platelet mitochondrial respiratory parameters. In conclusion, dietary saturated fatty acids above 9.3% of total caloric intake influenced the relationship between short-term PM2.5 exposure and platelet mitochondrial respiration. Further research is needed to understand these associations and their implications for cardiovascular health.

AggMapNet: enhanced and explainable low-sample omics deep learning with feature-aggregated multi-channel networks.

Omics-based biomedical learning frequently relies on data of high-dimensions (up to thousands) and low-sample sizes (dozens to hundreds), which challenges efficient deep learning (DL) algorithms, particularly for low-sample omics investigations. Here, an unsupervised novel feature aggregation tool AggMap was developed to Aggregate and Map omics features into multi-channel 2D spatial-correlated image-like feature maps (Fmaps) based on their intrinsic correlations. AggMap exhibits strong feature reconstruction capabilities on a randomized benchmark dataset, outperforming existing methods. With AggMap multi-channel Fmaps as inputs, newly-developed multi-channel DL AggMapNet models outperformed the state-of-the-art machine learning models on 18 low-sample omics benchmark tasks. AggMapNet exhibited better robustness in learning noisy data and disease classification. The AggMapNet explainable module Simply-explainer identified key metabolites and proteins for COVID-19 detections and severity predictions. The unsupervised AggMap algorithm of good feature restructuring abilities combined with supervised explainable AggMapNet architecture establish a pipeline for enhanced learning and interpretability of low-sample omics data.

Ligand-solvent coordination enables comprehensive trap passivation for efficient quantum dot near-infrared light-emitting diodes.

Near-infrared light-emitting diodes (NIR LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiency (EQE) of ~15%. However, these high-performance NIR-QLEDs suffer from immediate carrier quenching because of the accumulation of migratable ions at the surface of the QDs. These uncoordinated ions and carriers - if not bound to the nanocrystal surface - serve as centers for exciton quenching and device degradation. In this work, we overcome this issue and fabricate high-performance NIR QLEDs by devising a ligand anchoring strategy, which entails dissolving the strong-binding ligand (Guanidine Hydroiodide, GAI) in the mediate-polar solvent. By employing the dye-sensitized device structure (phosphorescent indicator), we demonstrate the elimination of the interface defects. The treated QDs films exhibit an exciton binding energy of 117 meV: this represents a 1.5-fold increase compared to that of the control (74 meV). We report, as a result, the NIR QLEDs with an EQE of 21% which is a record among NIR perovskite QLEDs. These QLEDs also exhibit a 7-fold higher operational stability than that of the best previously reported NIR QLEDs. Furthermore, we demonstrate that the QDs are compatible with large-area QLEDs: we showcase 900 mm2 QLEDs with EQE approaching 20%.

14-3-3ζ inhibits maladaptive repair in renal tubules by regulating YAP and reduces renal interstitial fibrosis.

Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.

Efficient Near-Infrared Electroluminescence from Lanthanide-Doped Perovskite Quantum Cutters.

Perovskite nanocrystals (PeNCs) deliver size- and composition-tunable luminescence of high efficiency and color purity in the visible range. However, attaining efficient electroluminescence (EL) in the near-infrared (NIR) region from PeNCs is challenging, limiting their potential applications. Here we demonstrate a highly efficient NIR light-emitting diode (LED) by doping ytterbium ions into a PeNCs host (Yb3+ : PeNCs), extending the EL wavelengths toward 1000 nm, which is achieved through a direct sensitization of Yb3+ ions by the PeNC host. Efficient quantum-cutting processes enable high photoluminescence quantum yields (PLQYs) of up to 126 % from the Yb3+ : PeNCs. Through halide-composition engineering and surface passivation to improve both PLQY and charge-transport balance, we demonstrate an efficient NIR LED with a peak external quantum efficiency of 7.7 % at a central wavelength of 990 nm, representing the most efficient perovskite-based LEDs with emission wavelengths beyond 850 nm.

Iodotrimethylsilane as a Reactive Ligand for Surface Etching and Passivation of Perovskite Nanocrystals toward Efficient Pure-red to Deep-red LEDs.

Resurfacing perovskite nanocrystals (NCs) with tight-binding and conductive ligands to resolve the dynamic ligands-surface interaction is the fundamental issue for their applications in perovskite light-emitting diodes (PeLEDs). Although various types of surface ligands have been proposed, these ligands either exhibit weak Lewis acid/base interactions or need high polar solvents for dissolution and passivation, resulting in a compromise in the efficiency and stability of PeLEDs. Herein, we report a chemically reactive agent (Iodotrimethylsilane, TMIS) to address the trade-off among conductivity, solubility and passivation using all-inorganic CsPbI3 NCs. The liquid TMIS ensures good solubility in non-polar solvents and reacts with oleate ligands and produces in situ HI for surface etching and passivation, enabling strong-binding ligands on the NCs surface. We report, as a result, red PeLEDs with an external quantum efficiency (EQE) of ≈23 %, which is 11.2-fold higher than the control, and is among the highest CsPbI3 PeLEDs. We further demonstrate the universality of this ligand strategy in the pure bromide system (CsPbBr3 ), and report EQE of ≈20 % at 640, 652, and 664 nm. This represents the first demonstration of a chemically reactive ligand strategy that applies to different systems and works effectively in red PeLEDs spanning emission from pure-red to deep-red.

Interruption of the long non-coding RNA HOTAIR signaling axis ameliorates chemotherapy-induced cachexia in bladder cancer.

BACKGROUND: Cisplatin-based chemotherapy is the first line of treatment for bladder cancer. However, cisplatin induces muscle wasting associated with NF-κB and cancer cachexia. HOTAIR, an oncogenic long non-coding RNA (lncRNA), promotes cancer progression in different cancers. Crosstalk between HOTAIR and NF-κB is documented. Prothymosin α (ProT) plays important roles in cancer progression and inflammation. However, the potential link between HOTAIR, ProT, and cisplatin-induced cancer cachexia remains unexplored. Here, we investigated the contribution of HOTAIR in cisplatin-induced cancer cachexia and dissected the potential signaling cascade involving the epidermal growth factor receptor (EGFR), ProT, NF-κB, and HOTAIR. MATERIALS AND METHODS: Expression of ProT and HOTAIR transcripts and their correlations in tumor tissues of bladder cancer patients and bladder cancer cell lines were determined by RT-qPCR. Next, levels of phospho-EGFR, EGFR, phospho-NF-κB, and NF-κB were examined by immunoblot analysis in human bladder cancer cells treated with cisplatin. Expression of HOTAIR in cisplatin-treated cells was also assessed by RT-qPCR. Pharmacological inhibitors and overexpression and knockdown approaches were exploited to decipher the signaling pathway. The murine C2C12 myoblasts were used as an in vitro muscle atrophy model. The syngeneic murine MBT-2 bladder tumor was used to investigate the role of mouse Hotair in cisplatin-induced cancer cachexia. RESULTS: Expression of ProT and HOTAIR was higher in bladder tumors than in normal adjacent tissues. There were positive correlations between ProT and HOTAIR expression in clinical bladder tumors and bladder cancer cell lines. Cisplatin treatment increased EGFR and NF-κB activation and upregulated ProT and HOTAIR expression in bladder cancer cells. ProT overexpression increased, whereas ProT knockdown decreased, HOTAIR expression. Notably, cisplatin-induced HOTAIR upregulation was abrogated by EGFR inhibitors or ProT knockdown. ProT-induced HOTAIR overexpression was diminished by NF-κB inhibitors. HOTAIR overexpression enhanced, whereas its knockdown reduced, cell proliferation, cachexia-associated pro-inflammatory cytokine expression, and muscle atrophy. Cachexia-associated symptoms were ameliorated in mice bearing Hotair-knockdown bladder tumors undergoing cisplatin treatment. CONCLUSIONS: We demonstrate for the first time a critical role for HOTAIR and identify the involvement of the EGFR-ProT-NF-κB-HOTAIR signaling axis in cisplatin-induced cachexia in bladder cancer and likely other cancers. Our findings also provide therapeutic targets for this disease.

Omega-3 fatty acids attenuate cardiovascular effects of short-term exposure to ambient air pollution.

BACKGROUND: Exposure to air pollution is associated with elevated cardiovascular risk. Evidence shows that omega-3 polyunsaturated fatty acids (omega-3 PUFA) may attenuate the adverse cardiovascular effects of exposure to fine particulate matter (PM2.5). However, it is unclear whether habitual dietary intake of omega-3 PUFA protects against the cardiovascular effects of short-term exposure to low-level ambient air pollution in healthy participants. In the present study, sixty-two adults with low or high dietary omega-3 PUFA intake were enrolled. Blood lipids, markers of vascular inflammation, coagulation and fibrinolysis, and heart rate variability (HRV) and repolarization were repeatedly assessed in 5 sessions separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily PM2.5 and maximum 8-h ozone (O3) concentrations were obtained from nearby air quality monitoring stations. Linear mixed-effects models were used to assess the associations between air pollutant concentrations and cardiovascular responses stratified by the omega-3 intake levels. RESULTS: The average concentrations of ambient PM2.5 and O3 were well below the U.S. National Ambient Air Quality Standards during the study period. Significant associations between exposure to PM2.5 and changes in total cholesterol, von Willebrand factor (vWF), tissue plasminogen activator, D-dimer, and very-low frequency HRV were observed in the low omega-3 group, but not in the high group. Similarly, O3-associated adverse changes in cardiovascular biomarkers (total cholesterol, high-density lipoprotein, serum amyloid A, soluable intracellular adhesion molecule 1, and vWF) were mainly observed in the low omega-3 group. Lag-time-dependent biphasic changes were observed for some biomarkers. CONCLUSIONS: This study demonstrates associations between short-term exposure to PM2.5 and O3, at concentrations below regulatory standard, and subclinical cardiovascular responses, and that dietary omega-3 PUFA consumption may provide protection against such cardiovascular effects in healthy adults.

The Integrity of Heme Is Essential for Reproducible Detection of Metronidazole-Resistant Clostridioides difficile by Agar Dilution Susceptibility Tests.

Metronidazole resistance in clinical Clostridioides difficile is often described as unstable, since resistant strains reportedly appear susceptible following freezer storage or brief passage. This has presented a conundrum for adopting susceptibility testing to accurately evaluate the connection between metronidazole resistance and decreased clinical efficacy of metronidazole in patients with C. difficile infections (CDIs). We discovered that supplementation of microbiological media with the metalloporphyrin heme is crucial for detection of metronidazole-resistant C. difficile using the agar dilution susceptibility testing method. Known metronidazole-resistant strains appeared susceptible to metronidazole in media lacking heme. Similarly, these resistant strains exhibited increased susceptibility to metronidazole when tested on heme-containing agars that were exposed to room light for more than 1 day, likely due to heme photodecomposition. In parallel experiments, resistance was reproducibly detected when heme-containing agars were either prepared and used on the same day or protected from light and then used on subsequent days. Notably, heme did not influence the susceptibilities of drug-susceptible strains that were of the same ribotype as the resistant strains. These findings firmly show that the consistent detection of metronidazole-resistant C. difficile is dependent upon heme and its protection from light. Studies are warranted to determine the extent to which this heme-associated metronidazole-resistant phenotype affects the clinical efficacy of metronidazole in CDI and the underlying genetic and biochemical mechanisms.

The influence of dietary intake of omega-3 polyunsaturated fatty acids on the association between short-term exposure to ambient nitrogen dioxide and respiratory and cardiovascular outcomes among healthy adults.

BACKGROUND: Short-term exposure to ambient nitrogen dioxide (NO2) is associated with adverse respiratory and cardiovascular outcomes. Supplementation of omega-3 polyunsaturated fatty acids (PUFA) has shown protection against exposure to fine particulate matter. This study aims to investigate whether habitual omega-3 PUFA intake differentially modify the associations between respiratory and cardiovascular responses and short-term exposure to ambient NO2. METHODS: Sixty-two healthy participants were enrolled into low or high omega-3 groups based on their habitual omega-3 PUFA intake. Each participant was repeatedly assessed for lung function, blood lipids, markers of coagulation and fibrinolysis, vascular function, and heart rate variability (HRV) in up to five sessions, each separated by at least 7 days. This study was carried out in the Research Triangle area of North Carolina, USA between October 2016 and September 2019. Daily ambient NO2 concentrations were obtained from an area air quality monitoring station on the day of outcome assessment (Lag0), 4 days prior (Lag1-4), as well as 5-day moving average (5dMA). The associations between short-term exposure to NO2 and the measured indices were evaluated using linear mixed-effects models stratified by omega-3 levels and adjusted by covariates including relative humidity and temperature. RESULTS: The average concentration of ambient NO2 during the study periods was 5.3±3.8 ppb which was below the National Ambient Air Quality Standards (NAAQS). In the high omega-3 group, an interquartile range (IQR) increase in short-term NO2 concentrations was significantly associated with increased lung function [e.g. 1.2% (95%CI: 0.2%, 2.2%) in FVC at lag1, 2.6% (95%CI: 0.4%, 4.8%) in FEV1 at 5dMA], decreased blood lipids [e.g. -2.6% (95%CI: -4.4%, -0.9%) in total cholesterol at lag2, -3.1% (95%CI: -6.1%, 0.0%) in HDL at 5dMA, and -3.1% (95%CI: -5.5%, -0.7%) in LDL at lag2], improved vascular function [e.g. 8.9% (95%CI: 0.6%, 17.2%) increase in FMD and 43.1% (95%CI: -79.8%, -6.3%) decrease in endothelin-1 at 5dMA], and changed HRV parameters [e.g. -7.2% (95%CI: -13.6%, -0.8%) in HFn and 13.4% (95%CI: 0.2%, 28.3%) in LF/HF ratio at lag3]. In the low omega-3 group, an IQR increase in ambient NO2 was associated with elevations in coagulation markers (von Willebrand Factor, D-dimer) and a decrease in HRV (very-low frequency); however, null associations were observed between short-term NO2 exposure and changes in lung function, blood lipids, and vascular function. CONCLUSIONS: The results in this study imply that dietary omega-3 PUFA consumption may offer respiratory and vascular benefits in response to short-term exposure of healthy adults to NO2 levels below the NAAQS. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02921048 ).

A qualitative study on the development of pharmacist-managed clinics in Taiwan.

WHAT IS KNOWN AND OBJECTIVE: Pharmacist-managed clinics (PMCs) are established to solve drug-related problems and enhance the quality of care of ambulatory patients. Although the benefits of such services have been demonstrated, little is known about PMC operations, especially outside the United States. The aim of this study was to explore how PMCs were established and to discuss implementation issues of PMCs in Taiwan. METHODS: A purposive sample of pharmacists, pharmacy administrators and physicians involved with PMCs was recruited from hospitals of varying scales across Taiwan. Semi-structured, individual interviews were conducted to understand the perceptions of the clinical service of PMCs. Interviews were transcribed verbatim and analysed by thematic analysis to find underlying themes. RESULTS: A total of 12 pharmacists, 5 pharmacy administrators and 3 physicians from 8 institutions were interviewed. Pharmacists spent 4 to 20 h per week at PMCs, and the practice experiences of PMC ranged from 1 to 6 years. PMCs have been provided in these institutions for 4 to 11 years with an average volume of 28 h and 25 patient visits weekly. Study participants described influential factors in establishing PMCs, including clinical expertise, attitude towards patient care and trust building with collaborating physicians. Operational concerns in implementing PMCs included role clarifications, manpower shortage, inadequate advanced training or certification, regulatory issues and a lack of service promotion. WHAT IS NEW AND CONCLUSION: This research broadens the understanding of operating PMC services and reveals key requirements and concerns regarding the care model, which can be useful for other countries. Resolving perceived barriers and collecting other stakeholders' perspectives may reinforce the integration of PMCs into patient care in the future.

Constitutive expression of the cryptic vanGCd operon promotes vancomycin resistance in Clostridioides difficile clinical isolates.

OBJECTIVES: To describe, for the first time (to the best of our knowledge), the genetic mechanisms of vancomycin resistance in clinical isolates of Clostridioides difficile ribotype 027. METHODS: Clinical isolates and laboratory mutants were analysed: genomically to identify resistance mutations; by transcriptional analysis of vanGCd, the vancomycin resistance operon encoding lipid II d-alanine-d-serine that is less bound by vancomycin than native lipid II d-alanine-d-alanine; by imaging of vancomycin binding to cell walls; and for changes in vancomycin bactericidal activity and autolysis. RESULTS: Vancomycin-resistant laboratory mutants and clinical isolates acquired mutations to the vanSR two-component system that regulates vanGCd. The substitutions impaired VanSR's function, resulting in constitutive transcription of vanGCd. Resistance was reversed by silencing vanG, encoding d-alanine-d-serine ligase in the vanGCd operon. In resistant cells, vancomycin was less bound to the cell wall septum, the site where vancomycin interacts with lipid II. Vancomycin's bactericidal activity was reduced against clinical isolates and laboratory mutants (64 and ≥1024 mg/L, respectively) compared with WT strains (4 mg/L). Truncation of the potassium transporter TrkA occurred in laboratory mutants, which were refractory to autolysis, accounting for their survival in high drug concentrations. CONCLUSIONS: Ribotype 027 evolved first-step resistance to vancomycin by constitutively expressing vanGCd, which is otherwise silent. Experimental evolutions and bactericidal assays show that ribotype 027 can acquire mutations to drastically enhance its tolerance to vancomycin. Thus, further epidemiological studies are warranted to examine the extent to which vancomycin resistance impacts clinical outcomes and the potential for these strains to evolve higher-level resistance, which would be devastating.

Co-existence of Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions: A case report.

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co-existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20-year-old woman who initially had co-existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre-existing skin lesions progress.

Effective disinfection of airborne microbial contamination in hospital wards using a zero-valent nano-silver/TiO2 -chitosan composite.

A novel antimicrobial composite of zero-valent silver nanoparticles (AgNPs), titania (TiO2 ), and chitosan (CS) was prepared via photochemical deposition of AgNPs on a CS-TiO2 matrix (AgNPs@CS-TiO2 ). Electron microscopy showed that the AgNPs were well dispersed on the CS-TiO2 , with diameters of 6.69-8.84 nm. X-ray photoelectron spectra indicated that most of the AgNPs were reduced to metallic Ag. Fourier-transform infrared spectroscopy indicated that some AgNPs formed a chelate with CS through coordination of Ag+ with the CS amide II groups. The zones of inhibition of AgNPs@CS-TiO2 for bacteria (Escherichia coli and Staphylococcus epidermidis) and fungi (Aspergillus niger and Penicillium spinulosum) were 6.72-11.08 and 5.45-5.77 mm, respectively, and the minimum (critical) concentrations of AgNPs required to inhibit the growth of bacteria and fungi were 7.57 and 16.51 µg-Ag/mm2 , respectively. The removal efficiency of a AgNPs@TiO2 -CS bed filter for bioaerosols (η) increased with the packing depth, and the optimal filter quality (qF) occurred for packing depths of 2-4 cm (qF = 0.0285-0.103 Pa-1 ; η = 57.6%-98.2%). When AgNPs@TiO2 -CS bed filters were installed in the ventilation systems of hospital wards, up to 88% of bacteria and 97% of fungi were removed within 30 minutes. Consequently, AgNPs@TiO2 -CS has promising potentials in bioaerosol purification.

Macrophage depletion with clodronate-containing liposomes affects the incidence and development of rheumatoid arthritis.

OBJECTIVE: This study investigated the effect of macrophage depletion with clodronate-containing liposomes (Clo-lip) on the incidence and development of rheumatoid arthritis (RA). METHODS: The effect of macrophage depletion with Clo-lip in the spleen was assessed by HE (haematoxylin and eosin) staining and immunohistochemistry (IHC). Thirty BALB/c mice were randomly divided into three groups, which were administered PBS-lip, Clo-lip, or normal saline. RA model mice were then created and the appearance of the paws was observed. Expression of CD68 by macrophages was examined by immunofluorescence on the 49th day. Forty-five RA model mice were created and randomly divided into three groups. The experiment group was administered Clo-lip at different timepoints. The degree of arthritis score was recorded during the administration. Histological features were detected by HE staining on the 84th day. RESULTS: Compared to controls, horseshoe-shaped nuclei and multi-core large cells were reduced in the experimental group (HE stain; p < 0.05). Brown tag-CD68 and tag-CD80 macrophages were fewer in the experimental group than in the control group (immunohistochemistry; p < 0.05). Furthermore, the degree of arthritis score in the experimental group was significantly decreased (p < 0.05). HE staining showed that there was no or less inflammatory cell infiltration in the articular cavity in mice in the experimental group, and that the percentage of CD68+ macrophage cells in synovial cells was significantly lower than in the control group (p < 0.05). CONCLUSION: Macrophage depletion with Clo-lip can affect the incidence and development of RA.

Nutrient Regulation: Conjugated Linoleic Acid's Inflammatory and Browning Properties in Adipose Tissue.

Obesity is the most widespread nutritional disease in the United States. Developing effective and safe strategies to manage excess body weight is therefore of paramount importance. One potential strategy to reduce obesity is to consume conjugated linoleic acid (CLA) supplements containing isomers cis-9, trans-11 and trans-10, cis-12, or trans-10, cis-12 alone. Proposed antiobesity mechanisms of CLA include regulation of (a) adipogenesis, (b) lipid metabolism, (c) inflammation, (d) adipocyte apoptosis, (e) browning or beiging of adipose tissue, and (f) energy metabolism. However, causality of CLA-mediated responses to body fat loss, particularly the linkage between inflammation, thermogenesis, and energy metabolism, is unclear. This review examines whether CLA's antiobesity properties are due to inflammatory signaling and considers CLA's linkage with lipogenesis, lipolysis, thermogenesis, and browning of white and brown adipose tissue. We propose a series of questions and studies to interrogate the role of the sympathetic nervous system in mediating CLA's antiobesity properties.

[Screening and follow-up for congenital heart disease in children aged 0-3 years in rural areas of Chongqing, China].

OBJECTIVE: To examine the incidence of congenital heart disease (CHD) in children aged 0-3 years in the rural areas of Chongqing, and to determine the suitable "screening-diagnosis-follow-up" system and screening indicators for CHD in these areas. METHODS: Children aged 0-3 years from rural areas of the Fuling Disctrict of Chongqing were selected by cluster sampling. Using the "screening-diagnosis-evaluation system" employed at the levels of village/town, district/county, and province/city, the children were screened for seven indicators, i.e., family history of CHD, dyspnea, cyanosis, unique facial features, other congenital malformations, heart murmurs, and blood oxygen saturation (SpO2<95%). Children who were positive for one or more indicators accepted echocardiography (ECG) for the diagnosis of CHD. CHD patients were evaluated for disease progression, given guided treatments, and followed-up by pediatric cardiologists. RESULTS: Screening was performed for 10 005 out of the 10 281 children enrolled in the study (97.32% response rate). Among the 175 children who were positive for the indicators, 166 underwent ECG and 60 (0.6‰) were diagnosed with CHD, including 46 cases of simple CHD (76.65%), 11 cases of combined CHD (18.33%), and 3 cases of complex CHD (5.00%). Of the 7 screening indicators, heart murmur had the largest area under the ROC curve for the diagnosis of CHD. In addition, a combination of screening indicators (heart murmur, unique facial features, and other congenital malformations) was most effective for screening out CHD. The CHD patients were given surgical or intervention treatments, and followed up for 6 to 18 months. Ten patients improved without treatment, 13 patients received interventional or surgical treatment, 1 patient died of non-cardiac reasons. The remaining 36 patients were subjected to further follow-up. CONCLUSIONS: Heart murmur alone and in combination with unique facial features and other congenital malformations are valuable tools for CHD screening in children aged 0-3 years. The "village/town-district/county-province/city" screening-diagnosis-evaluation systems are useful for the early detection, diagnosis, and treatment of CHD in infants and young children from the rural areas of Chongqing.

Intestinal and systemic inflammatory responses are positively associated with sulfidogenic bacteria abundance in high-fat-fed male C57BL/6J mice.

Recent studies have highlighted the relation between high-fat (HF) diets, the gut microbiota, and inflammation. However, the role of sulfidogenic bacteria in mediating these effects has been explored only recently. Therefore, we tested the hypothesis that an HF diet rich in saturated fat stimulates sulfidogenic bacteria and that these increases correlate with intestinal and systemic inflammatory responses. Forty C57BL/6J male mice were fed a low-fat (LF; 10% of energy) or an HF lard-based (60% of energy) diet for 6 or 20 wk. Mucosa samples were collected from the ileum, cecum, and colon and used for measuring 16S ribosomal RNA and functional genes of sulfidogenic bacteria. Matching intestinal samples and visceral and subcutaneous white adipose tissue (WAT) depots were used to measure mRNA abundance for inflammatory genes. Mice fed the HF diet had greater (P < 0.05) abundance of 3 types of sulfidogenic bacteria, primarily in colonic mucosa, compared with LF-fed mice at week 20. Although HF feeding did not increase intestinal inflammation at week 6, ileal markers of macrophage infiltration and inflammation were upregulated (P < 0.05) 1- to 6-fold at week 20. HF feeding impaired the localization of the tight junction protein zonula occludens 1 at the apical area of the ileal epithelium at weeks 6 and 20. Mice fed the HF diet had 1- to 100-fold greater (P < 0.05) mRNA levels of markers of macrophage infiltration in visceral and subcutaneous WAT at week 20, but not at week 6, compared with LF-fed mice. These results provide evidence that chronic, but not acute, consumption of an HF lard-based diet may be linked with pathways of microbial metabolism that potentially contribute to chronic intestinal and systemic inflammation. Such linkage provides further support for reducing consumption of saturated fats.