Search

Cutibacterium acnes (C. acnes) is a major pathogen implicated in the evolution of acne inflammation. Inhibition of C. acnes-induced inflammation is a prospective acne therapy strategy. Berberine (BBR), a safe and effective natural ingredient, has been proven to exhibit powerful antimicrobial and anti-inflammatory properties. However, the antimicrobial effect of BBR against C. acnes and its role in C. acnes-mediated inflammatory acne have not been explored. The objective of this investigation was to assess the antibacterial activity of BBR against C. acnes and its inhibitory effect on the inflammatory response. The results of in vitro experiments showed that BBR exhibited significant inhibition zones against four C. acnes strains, with the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in the range of 6.25–12.5 μg/mL and 12.5–25 μg/mL, respectively. On the bacterial growth curve, the BBR-treated C. acnes exhibited obvious growth inhibition. Transmission electron microscopy (TEM) images indicated that BBR treatment resulted in significant morphological changes in C. acnes. High-content imaging analysis further confirmed that BBR could effectively inhibit the proliferation of C. acnes. The disruption of cell wall and cell membrane structure by BBR treatment was preliminary confirmed according to the leakage of cellular contents such as potassium (K+), magnesium (Mg2+), and alkaline phosphatase (AKP). Furthermore, we found that BBR could reduce the transcript levels of genes associated with peptidoglycan synthesis (murC, murD, mraY, and murG). Meanwhile, we investigated the modulatory ability of BBR on C. acnes-induced skin inflammation in mice. The results showed that BBR effectively reduced the number of C. acnes colonized in mice’s ears, thereby alleviating ear swelling and erythema and significantly decreasing ear thickness and weight. In addition, BBR significantly decreased the levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in auricular tissues. These results suggest that BBR has the potential to treat inflammatory acne induced by C. acnes.

Background:Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear.Methods: The chemical composition of TFPCP was determined using UHPLC–Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%–20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics.Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1β); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-β1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites.Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.

In order to effectively control the stability of surrounding rock in ultra-large span open-off cuts by employing the techniques of support strength theory calculations and analogical application methods, two sets of rational support schemes were proposed, and the optimal design of active support parameters in thick coal seams with ultra-large span open-off cuts was explored by using theoretical analysis, numerical simulation, and field experiments. The results demonstrated that the span is one of the key factors influencing the stability of the roadway roof, exhibiting an inverse quadratic relationship with the peak stress borne by the roadway roof. By utilizing the pre-stressing force of anchor cables and support strength formulas, two sets of active support schemes for controlling the surrounding rock in thick coal seams with ultra-large span open-off cuts were established, and an optimized support scheme was obtained through numerical simulation. These findings provide references and guidance for related mining engineering under actual conditions in mines.

Abstract Background The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people’s attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. Methods This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. Results Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45–1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32–1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). Conclusions In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.

Abstract Background Canavalia rosea (Sw.) DC. (bay bean) is an extremophile halophyte that is widely distributed in coastal areas of the tropics and subtropics. Seawater and drought tolerance in this species may be facilitated by aquaporins (AQPs), channel proteins that transport water and small molecules across cell membranes and thereby maintain cellular water homeostasis in the face of abiotic stress. In C. rosea, AQP diversity, protein features, and their biological functions are still largely unknown. Results We describe the action of AQPs in C. rosea using evolutionary analyses coupled with promoter and expression analyses. A total of 37 AQPs were identified in the C. rosea genome and classified into five subgroups: 11 plasma membrane intrinsic proteins, 10 tonoplast intrinsic proteins, 11 Nod26-like intrinsic proteins, 4 small and basic intrinsic proteins, and 1 X-intrinsic protein. Analysis of RNA-Seq data and targeted qPCR revealed organ-specific expression of aquaporin genes and the involvement of some AQP members in adaptation of C. rosea to extreme coral reef environments. We also analyzed C. rosea sequences for phylogeny reconstruction, protein modeling, cellular localizations, and promoter analysis. Furthermore, one of PIP1 gene, CrPIP1;5, was identified as functional using a yeast expression system and transgenic overexpression in Arabidopsis. Conclusions Our results indicate that AQPs play an important role in C. rosea responses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role AQPs play in mediating C. rosea adaptation to extreme environments, but also improve our knowledge of plant aquaporin evolution more generally.

Objective To explore the role of high mobility group AT-hook 2 (HMGA2) in the regulation of the cell cycle and apoptosis. Methods The renal carcinoma cell line ACHN was transiently transfected with small interfering RNA to knock down the expression of the HMGA2 gene. Cell cycle analysis was undertaken using flow cytometry. The mRNA and protein levels of HMGA2, E2F transcription factor 1 (E2F1), cyclin D1, cyclin dependent kinase 6 (CDK6), B-cell lymphoma-2 (Bcl-2), caspase-3 and caspase-9 were analysed using reverse transcription quantitative real-time polymerase chain reaction and Western blot analysis. Results The mRNA and protein levels of HMGA2 were significantly higher in renal carcinoma cell lines compared with the human renal proximal tubular epithelial cell line HKC. After HMGA2 gene-specific silencing, more cells entered the G 0 /G 1 phase, while fewer cells entered the G 2 /M phase; and the cells exhibited early and late apoptosis. HMGA2 gene-specific silencing significantly reduced the mRNA and protein levels of E2F1, cyclin D1, CDK6 and Bcl-2; and increased the mRNA and protein levels of caspase-3 and caspase-9. Conclusion The HMGA2 gene may be involved in the tumorigenesis and development of renal cancer, thus inhibiting HMGA2 gene expression might provide a potential therapeutic target in the future.

Abstract Background Accurately differentiating pneumocystis from cytomegalovirus pneumonia is crucial for correct therapy selection in AIDS patients. Hence, the goal of this study was to compare the computerized tomography (CT) features of pneumocystis pneumonia and cytomegalovirus pneumonia in AIDS patients and identify clinical hallmarks to accurately distinguish these two pathologies. Methods A total of 112 AIDS patients (78 with pneumocystis pneumonia and 34 cytomegalovirus pneumonia) at Beijing Ditan Hospital from January 2017 to May 2019 were included in this study. Two experienced chest radiologists retrospectively reviewed CT images for 17 features including ground-glass opacity, consolidation, nodules, and halo sign. Binary logistic regression analyses were conducted to identify the significant parameters that distinguished pneumocystis pneumonia from cytomegalovirus pneumonia. Correlations were analyzed by Pearson or Spearman correlation analyses. Result were considered significant if P 0.05) were common in both groups. Conclusions Analysis of consolidation, nodules, and halo signs may contribute to the differential diagnosis of pneumocystis pneumonia or cytomegalovirus pneumonia. However, some CT features considered typical in one or other diseases appear with similar frequency in both cohorts of AIDS patients. CT features are potentially useful for the differential diagnosis of pneumocystis pneumonia and cytomegalovirus pneumonia in AIDS patients.

Abstract Background Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. Methods The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. Results The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR

Abstract Background Acute kidney injury (AKI) is a common complication among human immunodeficiency virus (HIV)-infected patients resulting in increased morbidity and mortality. Continuous renal replacement therapy (CRRT) is a useful method and instrument in critically ill patients with fluid overload and metabolic disarray, especially in those who are unable to tolerate the intermittent hemodialysis. However, the epidemiology, influence factors of CRRT and mortality in patients with HIV/AIDS are still unclear in China. This study aims to study the HIV-infected patients admitted in Intensive Care Unit (ICU) and explore the influence factors correlated with CRRT and their prognosis. Methods We performed a retrospective case-control study in the ICU of the Beijing Ditan Hospital Capital Medical University. From June 1, 2005 to May 31, 2017, 225 cases were enrolled in this clinical study. Results 122 (54.2%) patients were diagnosed with AKI during their stay in ICU, the number and percentage of AKI stage 1, 2 and 3 were 38 (31.1%), 21(17.2%) and 63(51.7%), respectively. 26.2% of AKI patients received CRRT during the stay of ICU. 56.25% CRRT patients died in ICU. The 28-day mortality was 62.5%, and the 90-day mortality was 75%. By univariate logistics analysis, it showed that higher likelihood of diagnosis for respiratory failure (OR = 7.333,95% CI 1.467–36.664, p = 0.015), higher likelihood of diagnosis for septic shock (OR = 1.005,95% CI 1.001–1.01, p = 0.018), and higher likelihood to use vasoactive agents (OR = 10.667,95% CI 1.743–65.271, p = 0.001), longer mechanical ventilation duration (OR = 1.011,95% CI 1.002–1.019, p = 0.011), higher likelihood for diagnosis for PCP (OR = 7.50,95% CI 1.288–43.687, p = 0.025), higher SOFA score at ICU admission (OR = 1.183,95% CI 1.012–1.383, p = 0.035), longer duration of CRRT (OR = 1.014,95% CI 1.001–1.028, p = 0.034) contributed to a higher mortality at ICU. The Cox Analysis for the cumulative survival of AKI 3 patients between the CRRT and non-CRRT groups shows no significant differences (p = 0.595). Conclusions There is a high incidence of AKI in HIV-infected patients admitted in our ICU. Patients with severe AKI were more prone to be admitted for CRRT and have a consequent poor prognosis.

Tumor‐derived extracellular vesicles (EVs) and their contents are involved in the development of human malignancies. Circular RNAs (circRNAs), enriched in EVs, can regulate diverse cellular processes by acting as microRNA (miRNA) sponges or through other mechanisms. In the present study, we explored the potential roles of circRNAs in EVs in the development of pancreatic ductal adenocarcinoma (PDAC). First, plasma was obtained from patients with PDAC (n = 8) and healthy volunteers (n = 8), and EVs were isolated by the ultracentrifugation method. Nanoparticle tracking analysis and transmission electron microscopy confirmed the size and form of the isolated EVs. The circRNA expression profiles of EVs were investigated by high‐throughput whole transcriptome sequencing. We then further validated the accuracy of the circRNA sequencing data by quantitative real‐time PCR analysis using plasma samples and PC cell lines, and subsequently performed bioinformatics analysis to reveal the potential functional roles of the differentially expressed circRNAs and to construct a circRNA‐miRNA interaction network to predict the target miRNAs of these circRNAs. Our work provides novel targets for further studies concerning the pathogenesis of PDAC.

Abstract P450 119 peroxygenase was found to catalyze the sulfoxidation of thioanisole and the sulfonation of sulfoxide in the presence of tert‐butyl hydroperoxide (TBHP) for the first time with turnover rates of 1549 min−1 and 196 min−1 respectively. Several mutants were designed to improve the peroxygenation activity and thioanisole specificity by site‐directed mutagenesis. The F153G/T213G mutant gave an increase of sulfoxide yield and a decrease of sulfone yield. Moreover the S148P/I161T/K199E/T214V mutant and the K199E mutant with acidic Glu residue contributed to improving the product ratio of sulfoxide to sulfone. Addition of short‐alkyl‐chain organic acids to the P450 119 peroxygenase‐catalyzed sulfur oxidation of thioanisole was investigated. Octanoic acid was found to induce a preferred sulfoxidation of thioanisole catalyzed by the F153G/T213G mutant to give approximately 2.4‐fold increase in turnover rate with a kcat value of 3687 min−1 relative to that of the wild‐type, and by the F153G mutant to give the R‐sulfoxide up to 30 % ee. The experimental control and the proposed mechanism for the P450 119 peroxygenase‐catalyzed sulfoxidation of thioanisole in the presence of octanoic acid suggested that octanoic acid could partially occupy the substrate pocket; meanwhile the F153G mutation could enhance the substrate specificity, which could lead to efficiently regulate the spatial orientation of thioanisole and facilitate the formation of Compound I. This is the most effective catalytic system for the P450 119 peroxygenase‐catalyzed sulfoxidation of thioanisole.

We reported that the complete genome sequence of SARS-Coronavirus-2 (SARS-CoV-2) was obtained from a cerebrospinal fluid (CSF) sample by ultrahigh-depth sequencing. Fourteen days after onset, seizures, maxillofacial convulsions, intractable hiccups and a significant increase in intracranial pressure developed in an adult coronavirus disease 2019 patient. The complete genome sequence of SARS-CoV-2 obtained from the cerebrospinal fluid indicates that SARS-CoV-2 can invade the central nervous system. In future, along with nervous system assessment, the pathogen genome detection and other indicators are needed for studying possible nervous system infection of SARS-CoV-2.

Background:YindanJiedu Granules (YDJDG) have been newly prescribed as a Chinese herbal formula. This study aimed to compare the efficacy of YDJDG and lopinavir-ritonavir in the treatment of coronavirus disease 2019 (COVID-19).Methods: Overall, 131 patients with COVID-19 were included in this study. In addition to standard care, 60 of these patients received YDJDG (YDJDG group) and 71 received lopinavir-ritonavir (lopinavir-ritonavir group). Propensity score matching (PSM) was used to match the characteristics of individuals in the two groups, while the Kaplan-Meier method was used to compare the proportion recovery observed.Results: Cox analysis revealed that YDJDG and CD4 ≥ 660 cells/µL were independent predictive factors of proportion recovery. At baseline, disease types differed between the YDJDG and lopinavir-ritonavir treatment groups. Furthermore, no significant adverse effects or toxicities relevant to YDJDG were observed. The median recovery time was 21 days in the YDJDG group and 27 days in the lopinavir-ritonavir group. After PSM (1:1), 50 patient pairs, YDJDG vs. lopinavir-ritonavir, were analyzed. In the YDJDG group, the proportion of recovered patients was remarkably higher than that observed in the lopinavir-ritonavir group (p = 0.0013), especially for those presenting mild/moderate disease type and CD4 < 660 cells/µL. In the YDJDG group, the mean duration of fever and pulmonary exudative lesions was significantly shorter than that observed in the lopinavir-ritonavir group (p = 0.0180 and p = 0.0028, respectively).Conclusion: YDJDG reveals the potential to hasten the recovery period in COVID-19 patients with mild/moderate disease type or CD4 < 660 cells/µL by shortening the mean duration of fever and pulmonary exudative lesions.

Plant metal tolerance proteins (MTPs) play key roles in heavy metal absorption and homeostasis in plants. By using genome-wide and phylogenetic approaches, the origin and diversification of MTPs from Canavalia rosea (Sw.) DC. was explored. Canavalia rosea (bay bean) is an extremophile halophyte with strong adaptability to seawater and drought and thereby shows specific metal tolerance with a potential phytoremediation ability. However, MTP genes in leguminous plants remain poorly understood. In our study, a total of 12 MTP genes were identified in C. rosea. Multiple sequence alignments showed that all CrMTP proteins possessed the conserved transmembrane domains (TM1 to TM6) and could be classified into three subfamilies: Zn-CDFs (five members), Fe/Zn-CDFs (five members), and Mn-CDFs (two members). Promoter cis-acting element analyses revealed that a distinct number and composition of heavy metal regulated elements and other stress-responsive elements existed in different promoter regions of CrMTPs. Analysis of transcriptome data revealed organ-specific expression of CrMTP genes and the involvement of this family in heavy metal stress responses and adaptation of C. rosea to extreme coral reef environments. Furthermore, the metal-specific activity of several functionally unknown CrMTPs was investigated in yeast. These results will contribute to uncovering the potential functions and molecular mechanisms of heavy metal absorption, translocation, and accumulation in C. rosea plants.

Aquaporins are channel proteins that facilitate the transmembrane transport of water and other small neutral molecules, thereby playing vital roles in maintaining water and nutrition homeostasis in the life activities of all organisms. Canavalia rosea, a seashore and mangrove-accompanied halophyte with strong adaptability to adversity in tropical and subtropical regions, is a good model for studying the molecular mechanisms underlying extreme saline-alkaline and drought stress tolerance in leguminous plants. In this study, a PIP2 gene (CrPIP2;3) was cloned from C. rosea, and its expression patterns and physiological roles in yeast and Arabidopsis thaliana heterologous expression systems under high salt-alkali and high osmotic stress conditions were examined. The expression of CrPIP2;3 at the transcriptional level in C. rosea was affected by high salinity and alkali, high osmotic stress, and abscisic acid treatment. In yeast, the expression of CrPIP2;3 enhanced salt/osmotic and oxidative sensitivity under high salt/osmotic and H2O2 stress. The overexpression of CrPIP2;3 in A. thaliana could enhance the survival and recovery of transgenic plants under drought stress, and the seed germination and seedling growth of the CrPIP2;3 OX (over-expression) lines showed slightly stronger tolerance to high salt/alkali than the wild-type. The transgenic plants also showed a higher response level to high-salinity and dehydration than the wild-type, mostly based on the up-regulated expression of salt/dehydration marker genes in A. thaliana plants. The reactive oxygen species (ROS) staining results indicated that the transgenic lines did not possess stronger ROS scavenging ability and stress tolerance than the wild-type under multiple stresses. The results confirmed that CrPIP2;3 is involved in the response of C. rosea to salt and drought, and primarily acts by mediating water homeostasis rather than by acting as an ROS transporter, thereby influencing physiological processes under various abiotic stresses in plants.

The dedicated short-range communication/wireless access for vehicular environment together with the fourth generation-long-term evolution technologies has been widely accepted as the most promising approaches to enhance the transportation safety. As pedestrians are still protected based on the traditional honking approach, the communication-based safety alert is questionable in the practical usage. In this article, a dedicated short-range communication/long-term evolution/WiFi-based vehicular system is developed to support the vehicle-to-vehicle and vehicle-to-pedestrian communication for the safety of vehicles and pedestrians. The implementation of the heterogeneous vehicle-to-vehicle/vehicle-to-pedestrian communication module is based on an IEEE 802.11a compliant communication module, integrated with the long-term evolution module and WiFi wireless interface. A collision estimation and safety alert module on smartphone is further designed and implemented to protect pedestrians. Various performance evaluation experiments are carried out under different scenarios via an uncontrolled approach, including the university campus, typical urban streets, and suburban districts. The packet delivery rate and end-to-end latency in each scenario are recorded and analyzed based on non-line-of-sight/line of sight cases. Experiment results reveal that IEEE 802.11p based vehicle-to-vehicle communication is unstable in the non-line-of-sight conditions, while the cellular-based performs better in the transmission reliability but has larger latency than IEEE 802.11p. The WiFi based vehicle-to-pedestrian communication is efficient when the transmission distance is less than 150 m.

Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (p=0.004). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, p=0.001), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (p

Conducting polymer nanostructures have received increasing attention in both fundamental research and various application fields in recent decades. Compared with bulk conducting polymers, conducting polymer nanostructures are expected to display improved performance in energy storage because of the unique properties arising from their nanoscaled size: high electrical conductivity, large surface area, short path lengths for the transport of ions, and high electrochemical activity. Template methods are emerging for a sort of facile, efficient, and highly controllable synthesis of conducting polymer nanostructures. This paper reviews template synthesis routes for conducting polymer nanostructures, including soft and hard template methods, as well as its mechanisms. The application of conducting polymer mesostructures in energy storage devices, such as supercapacitors and rechargeable batteries, are discussed.

The development and validation of a multiscopic near-infrared fluorescence (NIRF) probe, cinnamoyl-F-(D)L-F-(D)L-F-PEG-cyanine7 (cFlFlF-PEG-Cy7), that targets formyl peptide receptor on neutrophils using a mice ear inflammation model is described. Acute inflammation was induced in mice by topical application of phorbol-12-myristate-13-acetate to left ears 24 hours before probe administration. Noninvasive NIRF imaging was longitudinally performed up to 24 hours following probe injection. The in vivo neutrophil-targeting specificity of the probe was characterized by a blocking study with preadministration of excess nonfluorescent peptide cFlFlF-PEG and by an imaging study with a scrambled peptide probe cLFFFL-PEG-Cy7. NIRF imaging of mice injected with cinnamoyl-L-F-F-F-L-PEG-cyanine7 (cFlFlF-PEG-Cy7) revealed that the fluorescence intensity for inflamed left ears was approximately fourfold higher than that of control right ears at 24 hours postinjection. In comparison, the ratios acquired with the scrambled probe and from the blocking study were 1.5- and 2-fold at 24 hours postinjection, respectively. Moreover, a microscopic immunohistologic study confirmed that the NIRF signal of cFlFlF-PEG-Cy7 was associated with activated neutrophils in the inflammatory tissue. With this probe, in vivo neutrophil chemotaxis could be correlatively imaged macroscopically in live animals and microscopically at tissue and cellular levels.

We examine tropical rainfall from the Geophysical Fluid Dynamics Laboratory's Atmosphere Model version 4 (GFDL AM4) at three horizontal resolutions of 100 km, 50 km, and 25 km. The model produces more intense rainfall at finer resolutions, but a large discrepancy still exists between the simulated and the observed frequency distribution. We use a theoretical precipitation scaling diagnostic to examine the frequency distribution of the simulated rainfall. The scaling accurately produces the frequency distribution at moderate‐to‐high intensity (≥10 mm day−1). Intense tropical rainfall at finer resolutions is produced primarily from the increased contribution of resolved precipitation and enhanced updrafts. The model becomes more sensitive to the grid‐scale updrafts than local thermodynamics at high rain rates as the contribution from the resolved precipitation increases. Plain Language Summary: State of the art global scale climate models have horizontal resolutions of the order of tens of kilometers. However, these resolutions are much lower than the scales required to resolve tropical convection. This study investigates whether a resolution increase from 100 km to 25 km results in notable improvements in simulating tropical rainfall. Higher resolution simulations capture more intense rainfall events that are missed by their coarser counterparts. However, they struggle to capture the accurate frequency distribution of intense rainfall events. Results reported in this study underscore the importance of scrutinizing and carefully interpreting the outcomes of high‐resolution climate model simulations. Key Points: Tropical rainfall distribution is analyzed using simulations from the Geophysical Fluid Dynamics Laboratory's Atmosphere Model version 4 at three horizontal resolutions: 100 km, 50 km, and 25 kmIncreasing horizontal resolution yields more intense tropical rainfall but not the accurate frequency distributionTheoretical precipitation scaling accurately captures the frequency distribution of the simulated precipitation at moderate‐to‐high intensity [ABSTRACT FROM AUTHOR]

Background: Currently, effective therapeutic drugs for age-related macular degeneration (AMD) are urgently needed, and it is crucial to explore new treatment targets. The proteome is indispensable for exploring disease targets, so we conducted a Mendelian randomization (MR) of the proteome to identify new targets for AMD and its related subtypes. Methods: The plasma protein level data used in this study were obtained from two large-scale studies of protein quantitative trait loci (pQTL), comprising 35,559 and 54,219 samples, respectively. The expression quantitative trait loci (eQTL) data were sourced from eQTLGen and GTEx Version 8. The discovery set for AMD data and subtypes was derived from the FinnGen study, consisting of 9,721 AMD cases and 381,339 controls, 5,239 wet AMD cases and 273,920 controls, and 6,651 dry AMD cases and 272,504 controls. The replication set for AMD data was obtained from the study by Winkler TW et al., comprising 14,034 cases and 91,234 controls. Summary Mendelian randomization (SMR) analysis was employed to assess the association between QTL data and AMD and its subtypes, while colocalization analysis was performed to determine whether they share causal variants. Additionally, chemical exploration and molecular docking were utilized to validate potential drugs targeting the identified proteins. Results: SMR and colocalization analysis jointly identified risk-associated proteins for AMD and its subtypes, including 5 proteins (WARS1, BRD2, IL20RB, TGFB1, TNFRSF10A) associated with AMD, 2 proteins (WARS1, IL20RB) associated with Dry-AMD, and 9 proteins (COL10A1, WARS1, VTN, SDF2, LBP, CD226, TGFB1, TNFRSF10A, CSF2) associated with Wet-AMD. The results revealed potential therapeutic chemicals, and molecular docking indicated a good binding between the chemicals and protein structures. Conclusion: Proteome-wide MR have identified risk-associated proteins for AMD and its subtypes, suggesting that these proteins may serve as potential therapeutic targets worthy of further clinical investigation. [ABSTRACT FROM AUTHOR]

As the community increases climate model horizontal resolutions and experiments with removing moist convective parameterizations entirely, it is imperative to understand how these advances affect the InterTropical Convergence Zone (ITCZ). We investigate how the ITCZ responds to deactivating parameterized convection at two resolutions, 50 and 6 km, in fixed sea surface temperature, aquaplanet simulations with the NOAA GFDL AM4 atmospheric model. Disabling parameterized convection at 50 km resolution narrows the ITCZ and increases its precipitation minus evaporation (P–E) maximum by ∼78%, whereas at 6 km resolution doing so widens the ITCZ and decreases its P–E maximum by ∼50%. Using the column‐integrated moist static energy budget, we decompose these tropical P–E responses into contributions from changes in atmospheric energy input (AEI), gross moist stability, and gross moisture stratification. At 6 km, the ITCZ weakens due to increased gross moist stability. Disabling the convective parameterization at this finer resolution deepens the circulation, favoring more efficient poleward energy transport out of the deep tropics and reduced precipitation in the core of the ITCZ. Conversely, at 50 km the ITCZ strengthening is primarily driven by AEI, which in turn stems primarily from increased low cloud amount and thus longwave cloud radiative cooling in the Hadley cell subsiding branch. The Hadley circulation overturning intensifies to produce poleward energy fluxes that compensate the longwave cooling, yielding a stronger ITCZ. We further show that the low level diabatic heating profiles over the descending region are instrumental in understanding such diverse responses. Plain Language Summary: About one‐third of Earth's precipitation falls within a narrow band near the equator, the InterTropical Convergence Zone (ITCZ). In this study, we investigate two modeling choices that affect the ITCZ: (a) the horizontal resolution of the model and (b) the convective parameterization, which controls how heat and water ascend within thunderstorms and clouds. We conduct four simulations using an idealized climate model setup that assumes the globe is wholly ocean with unchanging surface temperatures. One pair of simulations is conducted at 50 km resolution and the other pair of simulations is conducted at 6 km resolution. Both pairs of simulations compare the ITCZ with and without an active convective parameterization. The ITCZ precipitation maximum nearly doubles when deactivating the convective parameterization at 50 km resolution, however, at 6 km resolution, the ITCZ precipitation maximum halves. The reasons for these disparate ITCZ changes relate to how much, and how efficiently, energy is transported by the Hadley circulation. Whereas at 50 km, deactivating the convective parameterization promotes low clouds that cool the subtropics, accelerating the Hadley circulation and raising precipitation, at 6 km, deactivating the convective parameterization instead increases the efficiency with which energy is transported by the Hadley circulation, reducing precipitation. Key Points: Disabling parameterized convection changes the InterTropical Convergence Zone (ITCZ) precipitation minus evaporation maximum by +78% and −50% at 50 and 6 km resolutionsDisabling parameterized convection at 6 km resolution deepens the Hadley circulation, increasing gross moist stabilityDisabling parameterized convection at 50 km resolution increases subtropical cloud radiative cooling, intensifying the Hadley circulation [ABSTRACT FROM AUTHOR]

Objective: We explore the pharmacodynamic targets of kaempferol in treating osteoporosis using transcriptomics and animal experiment. Methods: Firstly, we constructed an ovariectomized rat model (OVX). The anti-osteoporosis effect of kaempferol was evaluated by bone mineral density (BMD) and hematoxylin-eosin staining comprehensively. Moreover, differential genes between groups were screened by RNA sequencing technology (RNA-seq) for transcriptomics and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis were performed. Finally, partial results of transcriptomics were verified to detect the expression of the relevant gene expression by immunohistochemistry. Results: The pharmacodynamic findings indicated that the administration of kaempferol resulted in an elevation in BMD (P < .01) and a notable enhancement in tibia microstructural indices in the experimental rats (P < .01). The transcriptomic analysis revealed that NTN1, LTBP4, GSN, and EBF1 were identified as the principal targets for therapeutic intervention in osteoporosis. The results of animal experiments showed that kaempferol promoted osteogenesis and inhibited bone resorption by downregulating the protein expression of NTN1, LTBP4, GSN, and EBF1 (P< .01). Conclusion: Kaempferol enhances BMD levels, retards tibial bone loss with structural deterioration in OVX model rats, and promotes bone formation while curbing bone resorption through NTN1, LTBP4, GSN, and EBF1 protein down-regulation [ABSTRACT FROM AUTHOR]

Self-assembled monolayers (SAMs) have been successfully employed to enhance the efficiency of inverted perovskite solar cells (PSCs) and perovskite/silicon tandem solar cells due to their facile low-temperature processing and superior device performance. Nevertheless, depositing uniform and dense SAMs with high surface coverage on metal oxide substrates remains a critical challenge. In this work, we propose a holistic strategy to construct composite hole transport layers (HTLs) by co-adsorbing mixed SAMs (MeO-2PACz and 2PACz) onto the surface of the H2O2-modified NiOx layer. The results demonstrate that the conductivity of the NiOx bulk phase is enhanced due to the H2O2 modification, thereby facilitating carrier transport. Furthermore, the hydroxyl-rich NiOx surface promotes uniform and dense adsorption of mixed SAM molecules while enhancing their anchoring stability. In addition, the energy level alignment at the interface is improved due to the utilization of mixed SAMs in an optimized ratio. Furthermore, the perovskite film crystal growth is facilitated by the uniform and dense composite HTLs. As a result, the power conversion efficiency of PSCs based on composite HTLs is boosted from 22.26% to 23.16%, along with enhanced operational stability. This work highlights the importance of designing and constructing NiOx/SAM composite HTLs as an effective strategy for enhancing both the performance and stability of inverted PSCs. [ABSTRACT FROM AUTHOR]