Silencing siRNA microneedle patches versus silicone sheets in reducing post-surgical scars: a randomized single-blinded intra-individually controlled clinical trial.

BACKGROUND: A common complication of wounds is exuberant growth of fibrotic scar tissue, which can lead to hypertrophic scars or keloids. There are currently no treatments with good evidence for preventing excessive scar tissue formation. In this study, we explored the use of microneedle patches containing siRNA inhibiting SPARC mRNA in reducing the volume of post-surgical scars. OBJECTIVE: We aim to compare the differences in the volume of post-surgical scars between daily application of siRNA-embedded dissolving microneedle patches and silicone sheets. The primary study outcome measure was the 3D volume of scar elevation.Our hypothesis was that scar formation in the half of the wound treated with siRNA microneedle patches will be lesser, as reflected by a smaller 3D volume, as compared to the half treated with silicone sheets. METHODS: This was an 8-week, single-blinded intra-individually controlled randomised trial in a tertiary dermatological centre. Patients with two-week-old post-operative wounds were recruited. Each half of the scar was randomly assigned to the microneedle patch or silicone sheet. Three-dimensional (3D) volumes were obtained from the scars via a high-resolution scanner at day 0, 30 and 60. RESULTS: At day 30, scars treated with the microneedle patches had a lower geometric mean volume of 0.79mm3 when compared to scars treated with silicone sheets, with a difference in mean percentage volume reduction of 10.70%.At day 60, scars treated with the microneedle patches had a statistically significant lower volume (8.88mm3) when compared to the side treated with silicone sheets (12.77mm3, p=0.005), with a difference in mean percentage reduction of 9.66%. Additionally, there was also a statistically significant difference between the percentage reduction in scar volume, compared to baseline, on the side treated with microneedle patches (mean=83.78%) compared to the side treated with silicone sheets (mean=74.11%). CONCLUSIONS: There was a significantly greater reduction in the volume of post-surgical scars on the side treated with microneedle patches compared to the side treated with silicone sheets. This demonstrates the use of transdermal gene silencing technology for scar inhibition and that siRNA microneedle patches can be an effective and safe modality in the reduction of scar tissue formation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000558729, https://www.anzctr.org.au.

High Carriage of tetA, sul1, sul2 and bla TEM Resistance Genes among the Multidrug-resistant Uropathogenic Escherichia coli (UPEC) Strains from Malaysian Patients.

The rapid emergence of multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) strains pose a critical challenge in urinary tract infection (UTI) treatments. However, little work elucidated the resistance mechanisms of the MDR UPEC clinical strains in Malaysia. Therefore, this study aimed to determine the antimicrobial susceptibility profiles and the prevalence of antimicrobial resistance genes among the UPEC strains. Polymerase chain reactions were conducted to detect the presence of 6 antimicrobial resistance genes among 60 UPEC strains. Meanwhile, the antimicrobial resistance profiles against 9 antimicrobials were examined through the Kirby-Bauer disk diffusion method. In this study, the MDR isolates accounted for 40.0% (24/60), with the highest prevalence of resistance towards ampicillin (43/60; 71.7%), followed by tetracycline (31/60; 51.7%), nalidixic acid (30/60; 50.0%), co-trimoxazole (20/60, 33.3%), ciprofloxacin (19/60, 31.7%), levofloxacin (16/60, 21.6%) and chloramphenicol (10/60, 16.7%). In contrast, low resistance rates were observed among minocycline (1/60; 1.7%) and imipenem (0/60; 0.0%). bla TEM was the most prevalent gene (36/60; 60.0%), followed by tetA (27/60; 45.0%), sul2 (25/60; 41.7%), sul1 (13/60; 21.7%) and tetB (8/60; 13.3%). Surprisingly, bla SHV was not detected among the UPEC isolates. The MDR, ampicillin and tetracycline-resistant isolates were significantly associated with a higher prevalence of tetA, sul1, sul2 and bla TEM. In contrast, tetB displayed no significant relationship with any of the antimicrobials tested. The patient's age and gender were not the risk factors for the carriage of the resistance genes. Our findings identified the common resistance genes carried by the antimicrobial resistant UPEC isolates and provide valuable insights into developing the best antibiotic prescription regime to treat UTIs in our local scene.

Clinical Characteristics and Outcomes of Patients with Well-Differentiated Papillary Peritoneal Mesothelial Tumors.

PURPOSE: Well-differentiated papillary peritoneal mesothelial tumors (WDPMTs) are understudied and discrete from peritoneal mesotheliomas (PMs). We report clinicopathologic characteristics and outcomes of a large prospective WDPMT cohort. METHODS: Patients with WDPMT identified between August 2007 and December 2020 were followed through January 2023. Clinical characteristics and outcomes were annotated. Overall survival (OS) was assessed from pathologic diagnosis. Germline variants were analyzed, and targeted next-generation sequencing (NGS; MSK-IMPACT) data were compared to PMs and diffuse pleural mesotheliomas (DPMs). RESULTS: Among 54 patients, median age at diagnosis was 55 (range 20-76), 50% were female (n = 27), and 46% were smokers (n = 25; median 8 pack/years). Most (94%, n = 51) WDPMTs were found during surgical explorations for other indications, primarily other malignancies. Two patients underwent surgical resection for WDPMT; none received systemic therapy for WDPMT. Median OS was not reached (19/54; median follow up 4.5 years). Somatic NGS was available for 35% (19/54) of patients. TRAF7 alterations were enriched in WDPMT (89%; 17/19) compared with PM (0%; 0/50; p < 0.0001) and DPM (0%; 0/74; p < 0.0001). In WDPMT compared with PM and DPM, there were less BAP1 (0% [0/0] vs. 4% [8/50] vs. 46% [34/74]; p = 0.001 and p < 0.0001, respectively) and NF2 (0% [0/0] vs. 24% [12/50] vs. 31% [23/74]; p = 0.03 and p = 0.001 respectively) alterations. Pathogenic germline variants were present in 23% (4/17) of WDPMTs. CONCLUSIONS: Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM.

Team interaction behaviors correlates with team creativity among nursing students: Canonical correlation and moderation analyses.

BACKGROUND: Prior studies have indicated team members' interaction behaviors may predict creativity among nursing students. METHODS: This study investigated the correlation between interaction behaviors and creativity, both individual- and team-level, among nursing students. In this cross-sectional quantitative study, data were obtained from self-reported questionnaires. Individual creativity was assessed using the Torrance Tests of Creative Thinking scale; the perceived team interaction behavior and team creativity were assessed using validated instruments. Canonical correlation analysis was conducted to determine the overall correlation between interaction behaviors, and creativity, and the moderating effect of female proportion dominance was also examined. RESULTS: A total of 164 nursing students (84.1% female) arranged into 14 teams were included in this study. Canonical correlation analysis showed a positive correlation between interaction behaviors and creativity (correlation = 0.88). All dimensions of interactive behaviors were positively related to creativity dimensions. A stronger correlation to team creativity (correlation = 1) was found compared to individual creativity (correlation = 0.07). This study demonstrated that individual interactive behaviors including spontaneous communication and helping behavior predicted high team creativity. CONCLUSIONS: This insight may be valuable for nursing education programs seeking to foster creativity and effective teamwork. The potential moderating effect of female proportions on team interaction behaviors and creativity should be investigated further.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

Acute Ongoing Nociception Delays Recovery of Consciousness from Sevoflurane Anesthesia via a Midbrain Circuit.

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period.

On the architecture of starch granules revealed by iodine vapor binding and lintnerization. Part 1: Microscopic examinations.

Structural nature of glucan chains in the amorphous part of granular starch was examined by iodine vapor treatment and lintnerization. Four iodine-stained amylose-containing normal starches and their waxy counterparts were examined under a microscope before, during, and after lintnerization. The presence of amylose retarded the lintnerization rate. The degree of retardation correlated with the structural type of the amylopectin component, suggesting that potato amylopectin (type 4 structure) interacts with amylose in the granules, whereas in barley granules (type 1 structure) the interaction is very weak. The inclusion complexes with iodine were not degraded by the acid treatment. Therefore, the iodine-glucan chain complex formation could be used to study the structural nature of the flexible, amorphous parts of the starch granules. Indeed, at the end of lintnerization, when 20%-30% of the granules remained, substantial amounts of blue-stained complexes were washed out from the granules especially from amylose-containing barley and maize starch, but also from both normal and waxy cassava and potato starch. The complexation with iodine did not affect the rate of lintnerization. This suggested that single helical structures were present during lintnerization also in the absence of iodine and this conformation was the reason for the acid resistance.

Melatonin Rescues Influenza A Virus-Induced Cellular Energy Exhaustion via OMA1-OPA1-S in Acute Exacerbation of COPD.

Although rapid progression and a poor prognosis in influenza A virus (IAV) infection-induced acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are frequently associated with metabolic energy disorders, the underlying mechanisms and rescue strategies remain unknown. We herein demonstrated that the level of resting energy expenditure increased significantly in IAV-induced AECOPD patients and that cellular energy exhaustion emerged earlier and more significantly in IAV-infected primary COPD bronchial epithelial (pDHBE) cells. The differentially expressed genes were enriched in the oxidative phosphorylation (OXPHOS) pathway; additionally, we consistently uncovered much earlier ATP exhaustion, more severe mitochondrial structural destruction and dysfunction, and OXPHOS impairment in IAV-inoculated pDHBE cells, and these changes were rescued by melatonin. The level of OMA1-dependent cleavage of OPA1 in the mitochondrial inner membrane and the shift in energy metabolism from OXPHOS to glycolysis were significantly increased in IAV-infected pDHBE cells; however, these changes were rescued by OMA1-siRNA or melatonin further treatment. Collectively, our data revealed that melatonin rescued IAV-induced cellular energy exhaustion via OMA1-OPA1-S to improve the clinical prognosis in COPD. This treatment may serve as a potential therapeutic agent for patients in which AECOPD is induced by IAV.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Enhancing antioxidant levels and mitochondrial function in porcine oocyte maturation and embryonic development through notoginsenoside R1 supplementation.

This study examines the impact of Notoginsenoside R1 (NGR1), a compound from Panax notoginseng, on the maturation of porcine oocytes and their embryonic development, focusing on its effects on antioxidant levels and mitochondrial function. This study demonstrates that supplementing in vitro maturation (IVM) medium with NGR1 significantly enhances several biochemical parameters. These include elevated levels of glutathione (GSH), nuclear factor erythrocyte 2-related factor 2 (NRF2) and mRNA expression of catalase (CAT) and GPX. Concurrently, we observed a decrease in reactive oxygen species (ROS) levels and an increase in JC-1 immunofluorescence, mitochondrial distribution, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and nuclear NRF2 mRNA levels. Additionally, there was an increase in ATP production and lipid droplets (LDs) immunofluorescence. These biochemical improvements correlate with enhanced embryonic outcomes, including a higher blastocyst rate, increased total cell count, enhanced proliferative capacity and elevated octamer-binding transcription factor 4 (Oct4) and superoxide dismutase 2 (Sod2) gene expression. Furthermore, NGR1 supplementation resulted in decreased apoptosis, reduced caspase 3 (Cas3) and BCL2-Associated X (Bax) mRNA levels and decreased glucose-regulated protein 78 kD (GRP78) immunofluorescence in porcine oocytes undergoing in vitro maturation. These findings suggest that NGR1 plays a crucial role in promoting porcine oocyte maturation and subsequent embryonic development by providing antioxidant levels and mitochondrial protection.

Targeted Modulation of Redox and Immune Homeostasis in Acute Lung Injury Using a Thioether-Functionalized Dendrimer.

Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.

Moderating Effect of Daylight Exposure on the Relationship Between Physical Activity and Sleep in Patients with Upper Digestive Cancer: An Exploratory Study.

OBJECTIVES: To examine the moderating effect of daylight exposure on physical activity and objective sleep quality, using wearable actigraph devices. METHODS: We recruited 324 patients with either gastric or esophageal cancer. Actigraphs were used to measure all objective data including daylight exposure, physical activity, and sleep quality. Pearson's correlation coefficients were used to examine the relationships among demographic data, disease attributes, physical activity, daylight exposure, and sleep. The Hayes PROCESS macro with the regression bootstrapping method was employed to analyze the moderating effect of daylight exposure on the relationship between physical activity and sleep. RESULTS: Sleep efficiency correlated positively with physical activity, while "wake after sleep onset" correlated negatively with physical activity and mean lux. Mean lux and light >500 lux significantly moderated the association between physical activity and sleep efficiency (P = .002 in both cases). Similarly, mean lux and light >500 lux significantly moderated the association between physical activity and "wake after sleep onset" (P = .002 and .001, respectively). CONCLUSION: Both average daylight exposure and time of exposure to >500 lux act as moderators of physical activity and objective sleep quality in patients with gastric or esophageal cancer. Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality. IMPLICATIONS FOR NURSING PRACTICE: Healthcare practitioners should encourage patients with cancer to engage in daily outdoor physical activity. Further intervention studies are needed to verify the combined effect of daytime light exposure and physical activity on improving sleep quality.

The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis.

Inflammatory cytokines have crucial roles in the pathogenesis of tuberculosis (TB), and interleukin (IL)-27 and IL-35 have a pro-inflammatory and anti-inflammatory effect on many diseases, including infectious diseases. Therefore, we evaluated the relationship between IL-27 and IL-35 gene polymorphism, expression levels, and pulmonary TB (PTB) susceptibility. Nine single-nucleotide polymorphisms (SNPs) in the IL-27 gene (rs181206, rs153109, and rs17855750) and the IL-35 gene (rs4740, rs428253, rs9807813, rs2243123, rs2243135, and rs568408) were genotyped by the SNPscan technique in 497 patients with PTB and 501 controls. There was no significant difference regarding the genotype and allele frequencies of the above SNPs in the IL-27 and IL-35 genes between patients with PTB and controls. Haplotype analysis showed that the frequency of the GAC haplotype in the IL-35 gene was significantly decreased in patients with PTB when compared to controls (p = 0.036). Stratified analysis suggested that the frequency of the IL-27 rs17855750 GG genotype was significantly increased in patients with PTB with fever. Moreover, the lower frequency of the IL-35 rs568408 GA genotype was associated with drug-induced liver injury in patients with PTB. The IL-35 rs428253 GC genotype, as well as the rs4740 AA genotype and A allele, showed significant relationships with hypoproteinemia in patients with PTB. When compared with controls, the IL-27 level was significantly increased in patients with PTB. Taken together, IL-35 gene variation might contribute to a protective role on the susceptibility to PTB, and IL-27 and IL-35 gene polymorphisms were associated with several clinical manifestations of patients with PTB.

The survival outcome differs between left-sided colon cancer and middle/low rectal cancer after colorectal hepatic metastasectomy.

BACKGROUND: The clinical outcomes between left-sided colon cancer and middle/low rectal cancer seem to be different. This study aimed to examine the effect of primary tumor location regarding the left-sided colon and middle/low rectum on the overall survival (OS) of patients who underwent colorectal hepatic metastasectomy. METHODS: Patients who underwent colorectal hepatic metastasectomy were retrospectively enrolled. Patients were classified into 2 groups according to the primary tumor location (left-sided colon and middle/low rectum). Categorical variables were compared using the chi-square test or Fisher exact test, and continuous variables were analyzed using the Student t test. Survival was analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were analyzed by univariate and multivariate analyses using Cox proportional hazards regression models. RESULTS: Overall, 365 patients were enrolled. Patients with left-sided colon cancer had significantly better OS than those with middle/low rectal cancer (hazard ratio [HR], 0.725; P = .018), with median OS estimates of 48 and 38 months, respectively. In the subgroup analysis of RAS mutations, patients with left-sided colon cancer had significantly prolonged OS compared with those with middle/low rectum cancer (HR, 0.608; P = .034), with median OS estimates of 49 and 26 months, respectively. This observation was limited to patients with RAS mutations. CONCLUSION: According to our findings, patients with middle/low rectal cancer had poorer survival outcome and should not be categorized together with patients with left-sided colon cancer in terms of OS after colorectal hepatic metastasectomy.

Phosphodiesterase 8 (PDE8): Distribution and Cellular Expression and Association with Alzheimer's Disease.

Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.

Melatonin improves influenza virus infection-induced acute exacerbation of COPD by suppressing macrophage M1 polarization and apoptosis.

BACKGROUND: Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. METHODS: COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. RESULTS: The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1ß attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1ß/STAT1 signaling via MTs. CONCLUSIONS: These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1ß/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD.

Spatially varying defocus map estimation from a single image based on spatial aliasing sampling method.

In current optical systems, defocus blur is inevitable due to the constrained depth of field. However, it is difficult to accurately identify the defocus amount at each pixel position as the point spread function changes spatially. In this paper, we introduce a histogram-invariant spatial aliasing sampling method for reconstructing all-in-focus images, which addresses the challenge of insufficient pixel-level annotated samples, and subsequently introduces a high-resolution network for estimating spatially varying defocus maps from a single image. The accuracy of the proposed method is evaluated on various synthetic and real data. The experimental results demonstrate that our proposed model outperforms state-of-the-art methods for defocus map estimation significantly.

Cast versus Kirschner wire fixation in type II paediatric phalangeal neck fractures.

PURPOSE: To compare the outcomes of type II pediatric phalangeal neck fractures (PPNFs) treated with closed reduction and cast immobilization (CRCI) versus closed reduction percutaneous pinning (CRPP), and evaluated the clinical efficacy of conservative versus surgical treatment of type II PPNFs via meta-analysis. METHODS: Patients aged ≤ 14 years with type II PPNFs were divided into conservative (CRCI) and operative (CRPP) groups. Radiographs measured angulation and translation; hand function was assessed with total active range of motion (TAM) and Quick-DASH. Complication rates were also compared between the groups. A meta-analysis of conservative versus operative treatment confirmed the clinical results. Statistical analysis was performed using SPSS 26.0 and R studio 3.0 with two-tailed, chi-squared, and Mann-Whitney U or t-tests, P < 0.05. Meta-analysis used fixed or random effects models, calculating mean differences and odds ratios for outcomes, and assessing heterogeneity with I2 and Q tests. RESULTS: Final angulation (3.4° ± 3.7° and 4.9° ± 5.4° vs. 3.6° ± 3.7° and 4.2° ± 4.3°) and displacement (6.3% ± 5.8% and 5.7% ± 4.7% vs. 5.8% ± 5.5% and 3.2% ± 4.2%) in the coronal and sagittal planes were not different statistically between the conservative and surgical groups (P > 0.05), but improved significantly compared to preoperative values (P < 0.05). Although Quick-DASH scores were comparable in both groups (P = 0.105), conservatively treated patients had a significantly better TAM at the last follow-up visit (P = 0.005). The complication rates were 24.2% and 41.7% in the surgical and conservatively treated groups respectively (P = 0.162). However, the latter primarily experienced imaging-related complications, whereas the former experienced functional complications (P = 0.046). Our meta-analysis (n = 181 patients) also showed comparable functional (P = 0.49) and radiographic (P = 0.59) outcomes and complication rates (P = 0.21) between the surgical (94 patients) and conservative (87 patients) groups. CONCLUSIONS: Conservative and surgical treatments are both reliable and safe approaches for managing type II PPNF in children. However, conservatively treated patients generally experience similar radiographic outcomes, lower complication rates, and better functional outcomes than surgically treated ones.