Co-designing interventions to strengthen the primary health care system for the management of hypertension and type 2 diabetes in China.

Background: Policy makers and researchers are tasked with exploring ways to strengthen primary health care (PHC) to address the growing burden of non-communicable diseases (NCDs). This study aims to use a co-design approach (i.e., meaningful involvement of research end users in study planning and design) to develop PHC interventions to improve the management of hypertension and type 2 diabetes (T2DM) in four study sites in China. Methods: The study adopted a three-step co-design approach, including (1) a two-round Delphi panel with health system and NCD professionals to identify prioritised health system challenges, (2) three co-design workshops (in each study site) with local health administrators, PHC providers, and residents with hypertension and/or T2DM, respectively, to develop interventions and identify factors influencing implementation, and (3) another round of co-design workshops with local health administrators to summarise findings and reach consensus. Qualitative synthesis was conducted to analyse results from the workshops. Findings: Thirteen experts were involved in the two-round Delphi panel, which identified three prioritised health system challenges, including limited capacities of PHC providers, suboptimal service quality and evaluation mechanisms, and unreliable health information systems. The co-design workshops involved 116 local stakeholders in 16 sessions (four in each site), and developed three groups of interventions to address the challenges: (1) empowering PHC providers through on-the-job training for capacity building; (2) empowering patient communities through health education on healthy lifestyles and NCD self-management; and (3) empowering health administrators through local health data monitoring and strengthening governance for local PHC programs. Site-specific interventions were also considered to cater for different local contexts. Several recommendations were further identified for the implementation of these interventions, emphasising the importance of local customisation, community participation, and cross-sectoral collaborations. Interpretation: By engaging multiple stakeholders in priority setting and solution generation, this study summarised several key areas for change in health workforce, service delivery, and health information. Future research should examine the effectiveness and implementation of these interventions to improve NCD management in PHC in China. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757) and National Natural Science Foundation of China (72074065). Shangzhi Xiong is supported by University of New South Wales tuition fee scholarship.

MicroRNA-146a-5p protects retinal ganglion cells through reducing neuroinflammation in experimental glaucoma.

Neuroinflammation plays important roles in retinal ganglion cell (RGC) degeneration in glaucoma. MicroRNA-146 (miR-146) has been shown to regulate inflammatory response in neurodegenerative diseases. In this study, whether and how miR-146 could affect RGC injury in chronic ocular hypertension (COH) experimental glaucoma were investigated. We showed that in the members of miR-146 family only miR-146a-5p expression was upregulated in COH retinas. The upregulation of miR-146a-5p was observed in the activated microglia and Müller cells both in primary cultured conditions and in COH retinas, but mainly occurred in microglia. Overexpression of miR-146a-5p in COH retinas reduced the levels pro-inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines, which were further confirmed in the activated primary cultured microglia. Transfection of miR-146a-5p mimic increased the percentage of anti-inflammatory phenotype in the activated BV2 microglia, while transfection of miR-146a-5p inhibitor resulted in the opposite effects. Transfection of miR-146a-5p mimic/agomir inhibited the levels of interleukin-1 receptor associated kinase (IRAK1) and TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB subunit p65. Dual luciferase reporter gene assay confirmed that miR-146a-5p could directly target IRAK1 and TRAF6. Moreover, downregulation of IRAK1 and TRAF6 by siRNA techniques or blocking NF-κB by SN50 in cultured microglia reversed the miR-146a-5p inhibitor-induced changes of inflammatory cytokines. In COH retinas, overexpression of miR-146a-5p reduced RGC apoptosis, increased RGC survival, and partially rescued the amplitudes of photopic negative response. Our results demonstrate that overexpression of miR-146a-5p attenuates RGC injury in glaucoma by reducing neuroinflammation through downregulating IRAK1/TRAF6/NF-κB signaling pathway in microglia.

Neuroprotection of the P2X7 receptor antagonist A740003 on retinal ganglion cells in experimental glaucoma.

The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1ß and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.

Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes.

ABSTRACT: Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.

A near-infrared fluorescent probe with thiadiazole unit as key skeleton for ICT and ESIPT mechanism and effective detection of Cu2.

Fluorescent probe L-I was synthesized to demonstrate that 1,3,4-thiadiazole is an attractive moiety and could be utilized as positive hydrogen bond acceptor for excited state intramolecular proton transfer (ESIPT) processes, guider of electrons movement for intramolecular charge transfer (ICT) process and identify group for mental ions. Furthermore, dicyanoisophorone framework was employed to improve the fluorescence characteristics and near-infrared (NIR) fluorescent emission at 695 nm accompanied by a Stoke's shift as large as 260 nm was obtained. L-I could selectively detect Cu2+ over other analytes taking advantages of high sensitivity, fast response within 30 s and low detection limit (0.026 µM). More important, L-I exhibited good performance for detection of Cu2+ in actual water samples, food products, traditional Chinese medicine and for cell imaging which demonstrates practical significance in the fields of environmental monitor, food safety and biotechnology.

Construction and validation of m6A-related diagnostic model for psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory disease. N6-methyladenosine (m6A) is involved in numerous biological processes in both normal and diseased states. Herein, we aimed to explore the potential role of m6A regulators in the diagnosis of psoriasis and predict molecular mechanisms by which m6A regulators impact psoriasis. Methods: GSE30999 (170 human skin tissue samples) and GSE13355 (180 human skin tissue samples) were downloaded as the training analysis dataset and validation dataset respectively. M6A-related genes were obtained from the literature and their expression levels in GSE30999 samples were measured to identify M6A-related DEGs between psoriasis lesions (LS) and non-lesional lesions (NL). We identified m6A-related DEGs using differential expression analysis and assessed their interactions through correlation analysis and network construction. A logistic regression analysis followed by LASSO optimization was employed to select m6A-related DEGs for the construction of a diagnostic model. The performance of the model was validated using support vector machine (SVM) methodology with sigmoid kernel function and extensive cross-validation. Additionally, the correlation between m6A-related DEGs and immune cell infiltration was analyzed, as well as the association of these DEGs with psoriasis subtypes. Functional analysis of the m6A-related DEGs included the construction of regulatory networks involving miRNAs, transcription factors (TFs), and small-molecule drugs. The m6A modification patterns were also explored by examining the gene expression differences between psoriasis subtypes and their enriched biological pathways. Finally, the expression of significant m6A regulators involved in the diagnostic model was examined by RT-qPCR. Results: In this study, ten optimal m6A-related DEGs were identified, including FTO, IGF2BP2, METTL3, YTHDC1, ZC3H13, HNRNPC, IGF2BP3, LRPPRC, YTHDC2, and HNRNPA2B1. A diagnostic model based on these m6A-related DEGs was constructed, demonstrating high diagnostic accuracy with an area under the curve (AUC) in GSE30999 and GSE13355 of 0.974 and 0.730, respectively. Meanwhile, the expression level of m6A regulators verified by RT-qPCR was consistent with the results in GSE30999. The infiltration of activated mast cells and NK cells was significantly associated with all ten m6A-related DEGs in psoriasis. Among them, YTHDC1, HNRNPC, and FTO were targeted by most miRNAs and were regulated by nine related TFs. Therefore, patients may benefit from dorsomorphin and cyclosporine therapy. Between the two subgroups, 1,592 DEGs were identified, including LRPPRC and METTL3. These DEGs were predicted to be involved in neutrophil activation, cytokine-cytokine receptor interactions, and chemokine signaling pathways. Conclusions: A diagnostic model based on ten m6A-related DEGs in patients with psoriasis was constructed, which may provide early diagnostic biomarkers and therapeutic targets for psoriasis.

Rational synthesis of 1,3,4-thiadiazole based ESIPT-fluorescent probe for detection of Cu2+ and H2S in herbs, wine and fruits.

Here, 1,3,4-thiadiazole unit was employed as novel excited state intramolecular proton transfer (ESIPT) structure to prepare favorable fluorescent probe. High selectivity and rapid response to Cu2+ was obtained and the settling reaction was also used to recover ESIPT characteristics of probe to achieve sequential detection of H2S. Remarkable color change of solution from colorless to bright yellow and fluorescence emission from green to dark realized the visual detection of Cu2+ by naked eyes and transition of probe into portable fluorescent test strips. As expected, L-E could be utilized to quantitatively sense Cu2+ and H2S in different actual water and food samples including herbs, wine and fruits. The limits of detection for Cu2+ and H2S were as low as 34.5 nM and 38.6 nM. Also, probe L-E achieved real-time, portable, on-site quantitative detection of Cu2+ via a colorimeter and a smartphone platform with limit of detection to 90.3 nM.

Using routinely collected data to determine care cascades of hypertension and type-2 diabetes management in China: a cross-sectional study.

Background: China's National Essential Public Health Service Package (NEPHSP) aims to promote health for all at the primary health care level and includes a focus on hypertension and type-2 diabetes mellitus (T2DM). However, there are limited contemporary data to quantify the care cascades of hypertension and T2DM in primary health care. Methods: This cross-sectional study involved individual level linkage of routinely collected data from the NEPHSP, health insurance claims and hospital electronic health records, from four diverse regions in China, including Xiling District (central China), Wenchuan County (western), Acheng District and Jiao District (northern). We first compared numbers of people aged ≥35 with a recorded diagnosis of hypertension and T2DM against expected numbers derived from epidemiological data. We then constructed care cascades to assess the percentages (1) enrolled in the NEPHSP, (2) adherent to the follow-up care of NEPHSP, (3) receiving medication treatment, and (4) having hypertension and/or T2DM controlled. Findings: In the four regions, the total numbers of people aged ≥35 diagnosed of hypertension and T2DM from any data source were 149,176 and 50,828, respectively. This was estimated to be 46.0% (95% confidence interval [CI]: 45.8%-46.2%) and 45.6% (95% CI: 45.3%-45.9%) of the expected totals for hypertension and T2DM, respectively. Among those diagnosed, 65.4% (95% CI: 65.1%-65.6%) with hypertension and 66.1% (95% CI: 65.7%-66.5%) with T2DM were enrolled in the NEPHSP, respectively, in which 54.8% (95% CI: 54.5%-55.2%) with hypertension and 64.7% (95% CI: 64.1%-65.2%) with T2DM were adherent to the required services. Among those enrolled, the overall treatment rates were 70.8% (95% CI: 70.6%-71.1%) for hypertension and 82.2% (95% CI: 81.8%-82.6%) for T2DM. Among those treated, a further 80.9% (95% CI: 80.6%-81.2%) with hypertension and 73.9% (95% CI: 73.3%-74.4%) with T2DM achieved control. These results varied considerably across regions, with the northern sites showing relatively higher enrolment rates while the central site had higher control rates. Interpretation: Detection and control rates for hypertension and T2DM are suboptimal in these four regions of China. Further strategies are needed to improve people's enrolment in and adherence to the NEPHSP and strengthen care delivery processes. Of note, our estimations of the diagnosis rates for each region are based on national level large epidemiological data. The interpretation of these data needs caution due to potential bias caused by regional variations. Funding: This study is funded by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Diseases funding (APP1169757), and National Natural Science Foundation of China (72074065).

Prognostic model construction and target identification of Si-Wu-Tang against breast cancer.

The targets and mechanisms of Si-Wu-Tang (SWT) against (Breast cancer) BRCA were identified and a survival model and nomogram was construted by network pharmacology, bioinformatic analysis and in vitro experiments. A total of 72 anti-breast cancer SWT targets were selected, among which eleven genes (MAOA、SQLE、CACNA2D1、GLI1、RORB、ITGB3、TACR1、NR3C2、CA3、RBP4 and PTK6) were used to construct a novel prognostic model of breast cancer. The anti-breast cancer activity of SWT was related to the modulation of the receptor tyrosine kinases signaling pathways. Moreover, two compounds, mairin and senkyunone were found to bind directly to ITGB3 and RORB proteins. Finally, mRNA and protein expression of ITGB3 and RORB was observed to be significantly down-regulated after incubation of MCF-7 cells with SWT. Overall, our results indicated that mairin and senkyunone were the key ingredients present in SWT, and ITGB3 as well as RORB proteins were the major targets affected by SWT. The prognostic model can be used to predict the outcome of BRCA patients.

Exendin-4 promotes retinal ganglion cell survival and function by inhibiting calcium channels in experimental diabetes.

Progressive damage of retinal ganglion cells (RGCs) is observed in early diabetic retinopathy. Intracellular Ca2+ overload mediated by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is involved in neurodegeneration, whereas glucagon-like peptide-1 (GLP-1) provides neuroprotection. However, whether GLP-1 plays a neuroprotective role in diabetic retinas by modulating VGCCs remains unknown. We found that eye drops of exendin-4, a long-acting GLP-1 receptor (GLP-1R) agonist, prevented the increase of L-type Ca2+ current (ILCa) densities of RGCs induced by 4-week hyperglycemia and promoted RGC survival by suppressing L-type VGCC (L-VGCC) activity in streptozotocin-induced diabetic rats. Moreover, exendin-4-induced suppression of ILCa in RGCs may be mediated by a GLP-1R/Gs/cAMP-PKA/ryanodine/Ca2+/calmodulin/calcineurin/PP1 signaling pathway. Furthermore, exendin-4 functionally improved the light-evoked spiking ability of diabetic RGCs. These results suggest that GLP-1R activation enhances cAMP to PP1 signaling and that PP1 inactivates L-VGCCs by dephosphorylating them, thereby reducing Ca2+ influx, which could protect RGCs against excitotoxic Ca2+ overload.

Role of TNF-α-induced m6A RNA methylation in diseases: a comprehensive review.

Tumor Necrosis Factor-alpha (TNF-α) is ubiquitous in the human body and plays a significant role in various physiological and pathological processes. However, TNF-α-induced diseases remain poorly understood with limited efficacy due to the intricate nature of their mechanisms. N6-methyladenosine (m6A) methylation, a prevalent type of epigenetic modification of mRNA, primarily occurs at the post-transcriptional level and is involved in intranuclear and extranuclear mRNA metabolism. Evidence suggests that m6A methylation participates in TNF-α-induced diseases and signaling pathways associated with TNF-α. This review summarizes the involvement of TNF-α and m6A methylation regulators in various diseases, investigates the impact of m6A methylation on TNF-α-induced diseases, and puts forth potential therapeutic targets for treating TNF-α-induced diseases.

Phylogeny-Related Variations in Venomics: A Test in a Subset of Habu Snakes (Protobothrops).

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

Factors associated with the uptake of national essential public health service package for hypertension and type-2 diabetes management in China's primary health care system: a mixed-methods study.

Background: China launched the primary health care (PHC) system oriented National Essential Public Health Service Package (NEPHSP) in 2009, to combat health challenges including the increasing burden from hypertension and type-2 diabetes (T2DM). In this study, the PHC system was assessed to understand factors influencing the uptake of the NEPHSP for hypertension and T2DM management. Methods: A mixed-methods study was conducted in seven counties/districts from five provinces across the mainland of China. Data included a PHC facility level survey and interviews with policy makers, health administrators, PHC providers, and individuals with hypertension and/or T2DM. The facility survey used the World Health Organisation (WHO) service availability and readiness assessment questionnaire. Interviews were thematically analysed using the WHO health systems building blocks. Findings: A total of 518 facility surveys were collected with over 90% in rural settings (n = 474). Forty-eight in-depth individual interviews and 19 focus-group discussions were conducted across all sites. Triangulating the quantitative and qualitative data found that China's continuous political commitment to strengthening the PHC system led to improvements in workforce and infrastructure. Despite this, many barriers were identified, including insufficient and under-qualified PHC personnel, remaining gaps in medicines and equipment, fragmented health information systems, residents' low trust and utilization of PHC, challenges in coordinated and continuous care, and lack of cross-sectorial collaborations. Interpretation: The study findings provided recommendation for future PHC system strengthening, including improving the quality of NEPHSP delivery, facilitating resource-sharing across health facilities, establishing integrated care systems, and exploring mechanisms for better cross-sectorial engagement in health governance. Funding: The study is supported by National Health and Medical Research Council (NHMRC) Global Alliance for Chronic Disease funding (APP1169757).

Anionic ligand-induced chirality in perovskite nanoplatelets.

Perovskite materials passivated by chiral ligands have recently shown unique chiroptical activity with promising optoelectronic applications. However, the ligands have been limited to chiral amines. Here, chiral phosphate molecules have been exploited to synthesize CsPbBr3 nanoplatelets. The nanoplatelets showed a distinct circular dichroism signal and maintained their chiroptical properties after purification with anti-solvent.

Cyclic silicon waveguide four-mode converter for mode division multiplexing transmission.

In this paper, a novel cyclic mode converter (CMC) is proposed and fabricated to implement cyclic mode permutation (CMP) on-chip for differential mode delay and mode-dependent loss elimination in the mode division multiplexing (MDM) transmission system. Cascaded by three optimally designed mode converters that do not affect the non-target modes, the proposed CMC can realize the conversion of any input mode among the TE0/TE1/TM0/TM1 modes. The three-dimensional finite-difference time-domain (3D-FDTD) simulation results show that the insertion loss of our device is less than 0.59 dB, and the crosstalk of each mode is lower than -15 dB under the range of 1500-1600 nm. The flat spectral response of this CMC is maintained even in the presence of fabrication errors up to±10 nm, showing great robustness. The experimental results also prove that at the center wavelength of 1550 nm the measured insertion loss of each mode is below 2.22 dB, and the crosstalk of each mode is lower than -15 dB. The proposed CMC provides a new idea for effectively reducing link damage in the MDM transmission system.

Mild phototherapy mediated by manganese dioxide-loaded mesoporous polydopamine enhances immunotherapy against colorectal cancer.

One of the main challenges in applying the immune checkpoint blockade to treat colorectal cancer (CRC) is the immunosuppressive tumor microenvironment. Owing to its excellent cancer cell killing ability and immune activation, mild photothermal therapy (PTT) has shown bright promise to sensitize tumors to immune checkpoint inhibition through turning the immunologically "cold" tumors into "hot" ones. Herein, a mild photothermal effect-assisted theragnostic nanodrug (MnO2@MPDA-PEG NPs) is developed by incorporating MnO2 into PEGylated-mesoporous polydopamine nanoparticles (MPDA-PEG NPs). The presence of PEG endows the theragnostic nanodrug with high biostability. After accumulation in colorectal tumor, the theragnostic nanodrug responds to the tumor microenvironment, leading to the simultaneous release of Mn2+ which serves as a magnetic resonance imaging (MRI) contrast agent for tumor imaging. The released Mn2+ could also promote mild photothermal treatment-induced immune response, including the maturation of BMDC cells. In vivo antitumor studies on a CT26 model demonstrate that MnO2@MPDA-PEG NPs could be a promising dual-imaging theragnostic nanodrug to potentiate the systemic antitumor immunities.

Excitation wavelength-dependent photoluminescence decay of single quantum dots near plasmonic gold nanoparticles.

Changing the excitation wavelength is a simple but effective strategy to modulate the photophysical cha racteristics of colloidal quantum dots (QDs) near plasmonic nanostructures. It has been observed that the photoluminescence (PL) decay of QDs near plasmonic nanostructures differs when the excitation wavelength is varied, but the exact mechanism is still unclear today. Here, we studied the excitation wavelength dependence of the PL decay of CdSe/CdS core/shell QDs near plasmonic gold nanoparticles at the single QD level. With the aid of statistical science, we demonstrated that the PL decay of a single QD near gold nanoparticles is generally faster when the QD is excited spectrally close to the localized surface plasmon resonance of gold nanoparticles. This excitation wavelength dependence is mainly caused by the varied proportion of photons coming from biexciton emission, which is the result of different local electric field enhancement by gold nanoparticles upon excitation.

Signaling Mechanism for Modulation by GLP-1 and Exendin-4 of GABA Receptors on Rat Retinal Ganglion Cells.

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (Gs) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca2+]i of GCs through the IP3-sensitive pathway and was blocked in Ca2+-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct Gs/cAMP-PKA/IP3/Ca2+/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.

Efficacy and Safety of COVID-19 Vaccination in Older Adults: A Systematic Review and Meta-Analysis.

Objective: To analyze the differences in efficacy and safety of different types of novel coronavirus pneumonia (COVID-19) vaccines in different age groups (young adults and elderly). Methods: Randomized controlled trials (RCTs) on COVID-19 vaccine in PubMed, Embase, Web of Science, and Cochrane library were searched by computer, and eight eligible studies were analyzed. Meta-analysis was performed using Stata 16.0 and RevMan5.4 software. Results: The mean geometric titer (GMT) of the virus in the elderly was significantly higher than that in the placebo group (SMD = 0.91, 95% CI (0.68, 1.15), p < 0.01), presenting no obvious difference compared with the young adults (SMD = 0.19, 95% CI (0.38, 0.01), p = 0.06). Meanwhile, the effect of multiple vaccinations was better than that of single vaccination (SMD = 0.83, 95% CI (0.33, 1.34), p < 0.01). However, the number of adverse events (AEs) in the elderly was lower than that in the young adults (OR = 0.35, 95% CI (0.29, 0.42), p < 0.01). Conclusions: The immunization effect of COVID-19 vaccine in the elderly is obvious, especially after multiple vaccinations, and the incidence of AEs in the elderly is low, which proves that the vaccination of the elderly is safe and effective.

Enhanced Electrocatalytic Oxidation of Small Organic Molecules on Platinum-Gold Nanowires: Influence of the Surface Structure and Pt-Pt/Pt-Au Pair Site Density.

The electrochemical oxidation of small organic molecules (SOMs) such as methanol and glucose is a critical process and has relevant applications in fuel cells and sensors. A key challenge in SOM oxidation is the poisoning of the surface by carbon monoxide (CO) and other partially oxidized intermediates, which is attributed to the presence of Pt-Pt pair sites. A promising pathway for overcoming this challenge is to develop catalysts that selectively oxidize SOMs via "direct" pathways that do not form CO as a primary intermediate. In this report, we utilize an ambient, template-based approach to prepare PtAu alloy nanowires with tunable compositions. X-ray photoelectron spectroscopy measurements reveal that the surface composition matches that of the bulk composition after synthesis. Monte Carlo method simulations of the surface structure of PtAu alloys with varying coverage of oxygen adsorbates and varying degrees of oxygen adsorption strength reveal that oxygen adsorption under electrochemical conditions enriches the surface with Pt and a large fraction of Pt-Pt sites remain on the surface even with the Au content of up to 50%. Electrochemical properties and the catalytic performance measurements of the PtAu nanowires for the oxidation of methanol and glucose reveal that the mechanistic pathways that produce CO are suppressed by the addition of relatively small quantities of Au (∼10%), and CO formation can be completely suppressed by 50% Au. The suppression of CO formation with small quantities of Au suggests that the presence of Pt-Au pair sites may be more important in determining the mechanism of SOM oxidation rather than Pt-Pt pair site density.