Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

PPARδ agonist protects against osteoarthritis by activating AKT/mTOR signaling pathway-mediated autophagy.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and PPARs are involved in its pathogenesis; however, the specific mechanisms by which changes in PPARδ impact the OA pathogenesis yet to be discovered. The purpose of this study was to ascertain how PPARδ affects the onset and development of OA. In vitro, we found that PPARδ activation ameliorated apoptosis and extracellular matrix (ECM) degradation in OA chondrocytes stimulated by IL-1ß. In addition, PPARδ activation may modulate AKT/mTOR signaling to partially regulate chondrocyte autophagy and apoptosis. In vivo, injection of PPARδ agonist into the articular cavity improved ECM degradation, apoptosis and autophagy in rats OA models generated by destabilization medial meniscus (DMM), eventually delayed degeneration of articular cartilage. Thus, targeting PPARδ for OA treatment may be a possibility.

Characteristics of SARS-CoV-2 Omicron BA.5 variants in Shanghai after ending the zero-COVID policy in December 2022: a clinical and genomic analysis.

Introduction: An unprecedented surge of Omicron infections appeared nationwide in China in December 2022 after the adjustment of the COVID-19 response policy. Here, we report the clinical and genomic characteristics of SARS-CoV-2 infections among children in Shanghai during this outbreak. Methods: A total of 64 children with symptomatic COVID-19 were enrolled. SARS-CoV-2 whole genome sequences were obtained using next-generation sequencing (NGS) technology. Patient demographics and clinical characteristics were compared between variants. Phylogenetic tree, mutation spectrum, and the impact of unique mutations on SARS-CoV-2 proteins were analysed in silico. Results: The genomic monitoring revealed that the emerging BA.5.2.48 and BF.7.14 were the dominant variants. The BA.5.2.48 infections were more frequently observed to experience vomiting/diarrhea and less frequently present cough compared to the BF.7.14 infections among patients without comorbidities in the study. The high-frequency unique non-synonymous mutations were present in BA.5.2.48 (N:Q241K) and BF.7.14 (nsp2:V94L, nsp12:L247F, S:C1243F, ORF7a:H47Y) with respect to their parental lineages. Of these mutations, S:C1243F, nsp12:L247F, and ORF7a:H47Y protein were predicted to have a deleterious effect on the protein function. Besides, nsp2:V94L and nsp12:L247F were predicted to destabilize the proteins. Discussion: Further in vitro to in vivo studies are needed to verify the role of these specific mutations in viral fitness. In addition, continuous genomic monitoring and clinical manifestation assessments of the emerging variants will still be crucial for the effective responses to the ongoing COVID-19 pandemic.

Binding Strengths and Orientations in CO2 Adsorption on Cationic Scandium Oxides: Governing Factor Revealed by a Combined Infrared Spectroscopy and Theoretical Study.

Carbon dioxide (CO2) adsorption is a critical step to curbing carbon emissions from fossil fuel combustion. Among various options, transition metal oxides have received extensive attention as promising CO2 adsorbents due to their affordability and sustainability for large-scale use. Here, the nature of binding interactions between CO2 molecules and cationic scandium oxides of different sizes, i.e., ScO+, Sc2O2+, and Sc3O4+, is investigated by mass-selective infrared photodissociation spectroscopy combined with quantum chemical calculations. The well-accepted electrostatic considerations failed to provide explanations for the trend in the binding strengths and variations in the binding orientations between CO2 and metal sites of cationic scandium oxides. The importance of orbital interactions in the driving forces for CO2 adsorption on cationic scandium oxides was revealed by energy decomposition analyses. A molecular surface property, known as the local electron attachment energy, is introduced to elucidate the binding affinity and orientation-specific reactivity of cationic scandium oxides upon the CO2 attachment. This study not only reveals the governing factor in the binding behaviors of CO2 adsorption on cationic scandium oxides but also serves as an archetype for predicting and rationalizing favorable binding sites and orientations in extended surface-adsorbate systems.

Disease resistance features of the executor R gene Xa7 reveal novel insights into the interaction between rice and Xanthomonas oryzae pv. oryzae.

Bacterial blight (BB), caused by Xanthomonas oryzae pv. oryzae (Xoo), is a widespread and destructive disease in rice production. Previously, we cloned an executor R gene, Xa7, which confers durable and broad-spectrum resistance to BB. Here, we further confirmed that the transcription activator-like effector (TALE) AvrXa7 in Xoo strains could directly bind to the effector-binding element (EBE) in the promoter of the Xa7 gene. Other executor R genes (Xa7, Xa10, Xa23, and Xa27) driven by the promoter of the Xa7 gene could be activated by AvrXa7 and trigger the hypersensitive response (HR) in tobacco leaves. When the expression of the Xa23 gene was driven by the Xa7 promoter, the transgenic rice plants displayed a similar resistance spectrum as the Xa7 gene, demonstrating that the disease resistance characteristics of executor R genes are mainly determined by their induction patterns. Xa7 gene is induced locally by Xoo in the infected leaves, and its induction not only inhibited the growth of incompatible strains but also enhanced the resistance of rice plants to compatible strains, which overcame the shortcomings of its race-specific resistance. Transcriptome analysis of the Xa7 gene constitutive expression in rice plants displayed that Xa7-mediated disease resistance was related to the biosynthesis of lignin and thus enhanced resistance to Xoo. Overall, our results provided novel insights and important resources for further clarifying the molecular mechanisms of the executor R genes.

Effects of Aloe Gel on Lactating Women with Nipple Trauma.

Background: To investigate the efficacy of aloe gel in reducing pain and promoting wound healing in postpartum women with nipple trauma. Method: There were 80 postpartum women who took part in this study having developed nipple trauma during breastfeeding in the obstetrics department of a tertiary grade A hospital in Suzhou from January to December 2021. Postpartum women with nipple trauma whose hospital bed numbers ranged between 15 and 33 were included in the test group, whereas those whose hospital bed numbers ranged between 35 and 53 were included in the control group. Both groups received health education and breastfeeding guidance. The control group applied lanolin cream to their nipple trauma, whereas the test group used aloe gel. We used a nipple trauma severity assessment table to determine the severity of nipple trauma in lactating women and a Visual Analogue Scale (VAS) to determine the level of nipple pain and referred to the Traditional Chinese Medicine Standard for Diagnosis and Therapeutic Efficacy for Diseases and Syndromes to determine the healing time of their wounds. Results: The test group scored 3.70 ± 1.24 and 1.65 ± 0.74 points on the VAS on the first and third days following the intervention, whereas the control group scored 4.30 ± 0.94 and 2.23 ± 1.07 points, respectively. It took 3.75 ± 1.08 days and 4.45 ± 1.15 days for the nipple pain to completely disappear in the test group and the control group, respectively. The healing period for nipple trauma was 5.28 ± 1.26 days for the test group and 6.03 ± 1.61 days for the control group. All of the aforementioned distinctions were statistically significant (p < 0.05). Conclusions: Aloe gel can significantly alleviate the pain associated with nipple trauma in lactating women, accelerate wound healing, and reduce the duration of nipple trauma.

A Fully Self-Powered Ocean Wave Observation System Empowered by Natural Light Modulated by a Friction-Driven Polymer Network Liquid Crystal.

Conventional ocean wave observation instruments are powered by batteries, limiting the continuous observation time. Besides, the waste of batteries brings environmental contaminations. Triboelectric nanogenerators (TENGs) can reveal ocean wave information through their electrical output, taking the triboelectric charge as the information carrier. However, charge amplification is necessary, consuming additional energy. Herein, taking the photons rather than electrons as the information carrier, we developed a fully self-powered natural light-enabled sensing system for ocean wave monitoring by coupling two rotary-freestanding sliding TENGs (RFS-TENGs) and a polymer network liquid crystal (PNLC)-triggered optical system. The natural light is modulated by the PNLC driven by ocean wave-induced friction. With the assistance of a one-way bearing, the rise and fall of the wave will trigger different RFS-TENGs to power the PNLC in different voltage drops, leading to different transmitted natural light intensities. The wave height information can be obtained through the number of pulse signals with the same trough light intensity, while the wave period can be obtained through the duration between the same two sets of pulse signals. The effectiveness of the developed sensing paradigm in practical applications was verified by flume-based experiments, with the highest accuracies of 90.7% in wave height and 99.8% in wave period.

Eye signs as a novel risk predictor in pulmonary arterial hypertension associated with systemic lupus erythematosus.

OBJECTIVE: To investigate the role of eye signs in predicting poor outcomes in systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH). METHODS: This prospective observational study recruited patients diagnosed with SLE-PAH from Jan. 2021 to Dec. 2021 at the First Affiliated Hospital of Nanchang University; those with other potential causes of PAH were excluded. The evaluation of various parameters, such as N-terminal prohormone of brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), echocardiography, and risk stratification based on the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines, was conducted at intervals of every 1-3 months, and a 6-month follow-up period was observed. The primary outcome measure considered improvement if there was a decline in the risk stratification grade at the end point and unimproved if there was no decline. Conjunctival microvascular images were observed and recorded. RESULTS: A total of 29 SLE-PAH patients were enrolled, comprising 12 in the improved group and 17 in the nonimproved group. All SLE-PAH patients showed various manifestations of eye signs, including vessel twisting, dilation, ischaemic areas, haemorrhages, reticulum deformity, and wound spots. The nonimproved group exhibited significantly lower vessel density (VD) and microvascular flow index (MFI) of conjunctival microvascular images than the improved group. Correlation analysis revealed that VD displayed a negative correlation with the WHO-FC (r = -0.413, p = 0.026) and NT-proBNP (r = -0.472, p = 0.010), as well as a positive correlation with the 6MWD (r = 0.561, p = 0.002). Similarly, MFI exhibited a negative correlation with WHO-FC (r = -0.408, p = 0.028) and NT-proBNP (r = -0.472, p = 0.010) and a positive correlation with 6MWD (r = 0.157, p = 0.004). Multivariate logistic regression analysis indicated that VD (OR 10.11, 95% CI 1.95-52.36), MFI (OR 7.85, 95% CI 1.73-35.67), NT-proBNP, and 6MWD were influential factors in predicting the prognostic improvement of SLE-PAH patients. ROC curve analysis demonstrated that VD, MFI, 6MWD, and NT-proBNP (with respective AUC values of 0.83, 0.83, 0.76, and 0.90, respectively) possessed a sensitivity and specificity of 75 and 100%, as well as 83 and 100%, respectively. Regarding prognostic prediction, VD and MFI exhibited higher sensitivity than 6MWD, whereas MFI displayed higher sensitivity and specificity than NT-proBNP. CONCLUSION: SLE-PAH can lead to various conjunctival microvascular manifestations in which vascular density and microvascular flow index can be used to assess cardiopulmonary function and predict therapeutic efficacy and prognosis in SLE-PAH patients.

OsACA9, an Autoinhibited Ca2+-ATPase, Synergically Regulates Disease Resistance and Leaf Senescence in Rice.

Calcium (Ca2+) is a versatile intracellular second messenger that regulates several signaling pathways involved in growth, development, stress tolerance, and immune response in plants. Autoinhibited Ca2+-ATPases (ACAs) play an important role in the regulation of cellular Ca2+ homeostasis. Here, we systematically analyzed the putative OsACA family members in rice, and according to the phylogenetic tree of OsACAs, OsACA9 was clustered into a separated branch in which its homologous gene in Arabidopsis thaliana was reported to be involved in defense response. When the OsACA9 gene was knocked out by CRISPR/Cas9, significant accumulation of reactive oxygen species (ROS) was detected in the mutant lines. Meanwhile, the OsACA9 knock out lines showed enhanced disease resistance to both rice bacterial blight (BB) and bacterial leaf streak (BLS). In addition, compared to the wild-type (WT), the mutant lines displayed an early leaf senescence phenotype, and the agronomy traits of their plant height, panicle length, and grain yield were significantly decreased. Transcriptome analysis by RNA-Seq showed that the differentially expressed genes (DEGs) between WT and the Osaca9 mutant were mainly enriched in basal immune pathways and antibacterial metabolite synthesis pathways. Among them, multiple genes related to rice disease resistance, receptor-like cytoplasmic kinases (RLCKs) and cell wall-associated kinases (WAKs) genes were upregulated. Our results suggest that the Ca2+-ATPase OsACA9 may trigger oxidative burst in response to various pathogens and synergically regulate disease resistance and leaf senescence in rice.

Establishment and comparison of different procedures for modeling intrauterine adhesion in rats: A preliminary study.

The establishment of a stable animal model for intrauterine adhesion (IUA) can significantly enhance research on the pathogenesis and pathological changes of this disease, as well as on the development of innovative therapeutic approaches. In this study, three different modeling methods, including phenol mucilage combined mechanical scraping, ethanol combined mechanical scraping and ethanol modeling alone were designed. The morphological characteristics of the models were evaluated. The underlying mechanisms and fertility capacity of the ethanol modeling group were analyzed and compared to those of the sham surgery group. All three methods resulted in severe intrauterine adhesions, with ethanol being identified as a reliable modeling agent and was subsequently subjected to further evaluation. Immunohistochemistry and RT-PCR results indicated that the ethanol modeling group exhibited an increase in the degree of fibrosis and inflammation, as well as a significant reduction in endometrial thickness, gland number, vascularization, and endometrial receptivity, ultimately resulting in the loss of fertility capacity. The aforementioned findings indicate that the intrauterine perfusion of 95 % ethanol is efficacious in inducing the development of intrauterine adhesions in rats. Given its cost-effectiveness, efficacy, and stability in IUA formation, the use of 95 % ethanol intrauterine perfusion may serve as a novel platform for evaluating innovative anti-adhesion materials and bioengineered therapies.

Research trends on airway remodeling: A bibliometrics analysis.

Background: Airway remodeling is an essential pathological basis of respiratory diseases such as asthma and COPD, which is significantly related to pulmonary function and clinical symptoms. And pulmonary disease can be improved by regulating airway remodeling. This study aimed to establish a knowledge map of airway remodeling to clarify current research hotspots and future research trends. Methods: A comprehensive search was performed to analyze all relevant articles on airway remodeling using the Web of Science Core Collection Database from January 01, 2004 to June 03, 2023.2 reviewers screened the retrieved literature. Besides, the CiteSpace (6.2. R3) and VOSviewer (1.6.19) were utilized to visualize the research focus and trend regarding the effect of airway remodeling. Results: A total of 4077 articles about airway remodeling were retrieved. The United States is the country with the most published literature, underscoring the country's role in airway remodeling. In recent years, China has been the country with the fastest growth in the number of published literature, suggesting that China will play a more critical role in airway remodeling in the future. From the perspective of co-operation among countries, European co-operation was closer than Asian co-operation. The co-citation analysis showed that 98,313 citations were recorded in 3594 articles, and 25 clusters could be realized. In recent years, Burst detection shows that oxidative stress and epithelial-mesenchymal transition are hot words. Conclusions: Based on the bibliometric analysis of airway remodeling studies in the past 20 years, a multi-level knowledge structure map was drawn, it mainly includes countries, institutions, research fields, authors, journals, keywords and so on. The research directions represented by obstructive airway disease, PDGF-BB treatment of airway smooth muscle, allergen-induced airway remodeling, extracellular matrix, and non-coding RNA are the research hotspots in the field of airway remodeling. While the risk factors for airway remodeling, the application of new noninvasively assessing tools, biomarkers as well as The molecular mechanism represented by EMT and autophagy had been frontiers in recent years.

Role of exhaled hydrogen sulfide in the diagnosis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is often accompanied by increased excretion of hydrogen sulfide (H2S). This study aimed to explore the value of exhaled H2S in the diagnosis of CRC. METHODS: A total of 80 people with normal colonoscopy results and 57 patients with CRC were enrolled into the present observational cohort study. Exhaled oral and nasal H2S were detected by Nanocoulomb breath analyser. Results were compared between the two groups. Receiver operating characteristic (ROC) curves were analysed and area under the curves (AUCs) were calculated to assess the diagnostic value of exhaled H2S. Meanwhile, the clinicopathological features, including gender, lesion location and tumour staging of patients with CRC, were also collected and analysed. RESULTS: The amount of exhaled H2S from patients with CRC was significantly higher than that of those with normal colonoscopy results. The ROC curve showed an AUC value of 0.73 and 0.71 based on oral and nasal H2S detection, respectively. The exhaled H2S in patients with CRC was correlated with gender, lesion location and tumour progression, including depth of invasion, lymphatic metastasis and TNM (Tumor, Lymph Nodes, Metastasis) staging. CONCLUSION: Exhaled H2S analysis is a convenient and non-invasive detection method for diagnosing CRC, suggesting a potential role in population screening for CRC.

Efficacy of antibiotic prophylaxis for reducing capsular contracture in prosthesis-based breast surgery: a systemic review and meta-analysis.

Antibiotics Prophylaxis to prevent capsular contracture in prosthesis-based breast surgery is common in clinical practice. However, there is currently a dearth of high-quality evidence concerning the effectiveness of antibiotic usage in this field. To identify all pertinent studies prior to January 2023, a comprehensive literature search was conducted in the PubMed, Embase, Web of Science, Cochrane Library, and Medline databases. The extracted data was then subjected to meta-analysis. Fourteen studies were retained in the analysis. According to the results, perioperative antibiotic prophylaxis did not reduce the risk of capsular contracture (RR 1.15, 95% CI 0.82-1.59, p = 0.55) or surgical-site infection (RD 0.01, 95% CI - 0.01 to 0.03, p = 0.59) compared to nonantibiotic prophylaxis. There was no statistically significant difference between extended antibiotic prophylaxis and perioperative antibiotic prophylaxis in terms of preventing capsular contracture, whether calculated by patient numbers (RD 0.01, 95% CI - 0.01 to 0.02, p = 0.87) or by total procedures (RD 0.00, 95% CI - 0.00 to 0.01, p = 0.88), or controlling surgical-site infection (RR 1.05, 95% CI 0.77-1.44, p = 0.27). Additionally, topical antibiotic irrigation did not decrease the risk of infection (RR 0.61, 95% CI 0.34-1.08, p = 0.29) and capsular contracture, regardless of patient number (RR 0.41, 95% CI 0.27-0.63, p = 0.18) or total number of procedures (RR 1.29, 95% CI 0.73-2.28, p < 0.01). Current evidence revealed that both systemic and topical antibiotic prophylaxis may not provide benefits in preventing capsular contracture in prosthesis-based breast surgery. When the occurrence of surgical-site infections is minimized to the greatest extent, the administration of additional antibiotics for reducing capsular contracture should be carefully and judiciously considered.

Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China.

OBJECTIVE: To investigate characteristics associated with different COVID-19 outcomes of people with systemic lupus erythematosus (SLE) and COVID-19 during the second pandemic wave of COVID-19 in China. METHODS: In this retrospective study, people with SLE and COVID-19 who visited the First Affiliated Hospital of Nanchang University from December 2022 and February 2023 were subjected to this study. The three possible outcomes were listed in order of ordinal severity: (1) not hospitalized, (2) hospitalized but not receiving oxygenation, and (3) hospitalized with any ventilation or oxygenation. A multivariable ordinal logistic regression model was built to examine the association between COVID-19 severity and demographic traits, medications, comorbidities, and disease activity. Furthermore, among the 301 SLE patients included in our study, only two patients experienced mortality. In order to maintain statistical rigor, we have included these two deceased patients in the outcome measure of hospitalized with any ventilation or oxygenation. RESULTS: A total of 301 patients with SLE were enrolled in this study. The multivariate ordinal logistic regression analyses indicated that high SLE disease activity (vs remission; OR 39.04, 95% CI 3.08 to 494.44, p = .005) was associated with more severe outcomes. Three doses of COVID-19 vaccination (OR 0.19, 95% CI 0.07 to 0.51, p = .001), glucocorticoids dose (1-5 mg/day 0.14, 0.03 to 0.73, p = .020, and 6-9 mg/day 0.12, 0.02 to 0.61, p = .010), and more intensive immunosuppression drugs (0.34, 0.12 to 0.97, p = .044) were associated with better outcomes. In age-adjusted and sex-adjusted models, telitacicept (6.66, 1.35 to 32.86, p = .020) and rituximab (7.81, 1.87 to 32.66, p = .005) were associated with more severe outcomes. Hydroxychloroquine (0.47, 0.25 to 0.88, p = .018) was associated with favorable outcomes. CONCLUSION: Different COVID-19 outcomes in people with SLE are mostly driven by COVID-19 vaccination, medications, and activity SLE. More importantly, three doses of COVID-19 vaccination may be associated with better outcomes.

Emergence and high prevalence of unusual rotavirus G8P[8] strains in outpatients with acute gastroenteritis in Shanghai, China.

Group A rotavirus (RVA) is considered an important cause of acute gastroenteritis (AGE) in all age groups, especially in children. We investigated the epidemiology of RVA in outpatients aged ≤ 16 years at the Children's Hospital of Fudan University, Shanghai, China. In this study, 16.6% (246/1482) were infected with RVA. The detection rate of RVA was significantly higher in the year of 2021 (20.3%, 147/725) compared to the year of 2020 (14.5%, 77/531) and 2022 (9.7%, 22/226) (p = 0.000). RVA infection was prevalent in all seasons from 2020 to 2022, with a different monthly distribution observed in different years. Among 246 RVA-positive samples, 14 different RVA genotypes were detected with different frequencies. Overall, G9P[8] (45.5%, 112/246) was the most common RVA genotype, followed by G8P[8] (37.4%, 92/246) and G3P[8] (4.1%, 10/246). The prevalence of G/P combinations varied from 2020 to 2022. G9P[8] was the most prevalent circulating genotype in 2020 (68.2%, 15/22) and 2021 (57.8%, 85/147). However, G8P[8] (68.8%, 53/77) suddenly became the most prevalent genotype in 2022 after being first identified in 2020 and prevalent in 2021. The G8 strains detected in the study were all clustered to DS-1-like G8 strains with the closest genetic distance to strains circulating in Southeast Asia. Our study demonstrated the diversity of circulating RVA genotypes in Shanghai. The sudden emergence and high prevalence of unusual G8P[8] strains deserve more concern and indicate the need for continuous surveillance of RVA in children with AGE in the future to refine future vaccine strategy.

Retinal and Conjunctival Vessels in the Diagnosis and Assessment of Behcet's Disease: A New Approach.

BACKGROUND AND OBJECTIVE: The study aimed to investigate the alterations of retinal and conjunctival vessels in patients with Behcet's disease (BD). PATIENTS AND METHODS: In this case-control study, 17 patients (34 eyes) diagnosed with BD and 17 healthy volunteers (34 eyes) matched by age, sex, blood pressure, and intraocular pressure were recruited. Optical coherence tomography angiography examinations were performed to calculate the vessel density of the retina and conjunctiva according to different sizes of vessels and different zones divided by three segmentation methods of the retina: hemispheric segmentation, Early Treatment Diabetic Retinopathy Study, and central annulus segmentation. RESULTS: The vessel densities of the superficial macrovascular (P = 0.050), superficial microvascular (P < 0.001), superficial total microvascular (P < 0.001), deep total microvascular (P < 0.001), and deep total microvascular (P < 0.001) were significantly lower in the BD group. The conjunctival vessel density was significantly higher in the BD group (P < 0.001). The receiver operating characteristic curve analysis showed that the area under the curve of vessel density of the superior right (0.993, 95% CI 0.980-1) and right zones (0.996, 95% CI 0.987-1) were the largest in the superficial and deep retina, respectively. Otherwise, the area under the curve of conjunctival vessel density was 0.728 (95% CI 0.607-0.848). CONCLUSIONS: In patients with BD, retinal vessel density decreases, while conjunctival vessel density increases. Optical coherence tomography angiography provides a new noninvasive and quantitative assessment for retinal and conjunctival vessels. [Ophthalmic Surg Lasers Imaging Retina 2024;55:13-21.].

Identifying new safety risk of human serum albumin: a retrospective study of real-world data.

Objective: To mine and analyze the adverse reaction signals of human serum albumin (HSA) using the FDA adverse event reporting system (FAERS) database for the safe clinical use of this drug. Methods: Data cleaning and analysis of adverse event reports in the FAERS database for a total of 76 quarters from Q1 2004 to Q4 2022 were performed using the reporting odds ratio (ROR), Medicines and Healthcare Products Regulatory Agency (MHRA), and Bayesian confidence propagation neural network (BCPNN). Gender-differentiated signal detection was used to investigate the gender differences in the occurrence of HSA adverse events. Results: Through a combination of three methods, a total of 535 adverse event reports were identified. These reports involved 1,885 cases of adverse reactions, with respiratory, thoracic, and mediastinal disorders, as well as general disorders and administration site conditions, as the most common. One noteworthy new signal was the occurrence of transfusion-related acute lung injury. Additionally, gender-differentiated signals were present, with females experiencing paraesthesia, hypertension, pulmonary oedema, loss of consciousness, and vomiting. Conclusion: This study has revealed that HSA poses a risk of causing transfusion-related acute lung injury. It has also been observed that adverse reactions, including paraesthesia, hypertension, pulmonary oedema, loss of consciousness, and vomiting, are more prevalent in females. These findings should be taken into account when using HSA in a clinical setting.

Col1a1 mediates the focal adhesion pathway affecting hearing in miR-29a mouse model by RNA-seq analysis.

Age-related hearing loss (ARHL) is a common neurodegenerative disease. Its molecular mechanisms have not been fully elucidated. In the present study, we obtained differential mRNA expression in the cochlea of 2-month-old miR-29a+/+ mice and miR-29a-/- mice by RNA-seq. Gene ontology (GO) analysis was used to identify molecular functions associated with hearing in miR-29a-/- mice, including being actin binding (GO: 0003779) and immune processes. We focused on the intersection of differential genes, miR-29a target genes and the sensory perception of sound (GO:0007605) genes, with six mRNA at this intersection, and we selected Col1a1 as our target gene. We validated Col1a1 as the direct target of miR-29a by molecular and cellular experiments. Total 6 pathways involved in Col1a1 were identified by through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We selected the focal adhesion pathway as our target pathway based. Their expression levels in miR-29a-/- mice were verified by qRT-PCR and Western blot. Compared with miR-29a+/+ mice, the expression levels of Col1a1, Itga4, Itga2, Itgb3, Itgb7, Pik3r3 and Ptk2 were different in miR-29a-/- mice. Immunofluorescence was used to locate genes in the cochlea. Col1a1, Itga4 and Itgb3 were differentially expressed in the basilar membranes and stria vascularis and spiral ganglion neurons compared to miR-29a+/+ mice. Pik3r3 and Ptk2 were differentially expressed in the basilar membranes and stria vascularis, but not at the s spiral ganglion neurons compared to miR-29a+/+ mice. Our results show that when miR-29a is knocked out, the Col1a1 mediates the focal adhesion pathway may affect the hearing of miR-29a-/- mice. These findings may provide a new direction for effective treatment of age-related hearing loss.

Carbon dioxide activation by discandium dioxide cations in the gas phase: a combined investigation of infrared photodissociation spectroscopy and DFT calculations.

We present a combined computational and experimental study of CO2 activation at the Sc2O2+ metal oxide ion center in the gas phase. Density functional theory calculations on the structures of [Sc2O2(CO2)n]+ (n = 1-4) ion-molecule complexes reveal a typical end-on binding motif as well as bidentate and tridentate carbonate-containing configurations. As the number of attached CO2 molecules increases, activated forms tend to dominate the isomeric populations. Distortion energies are unveiled to account for the conversion barriers from molecularly bound isomers to carbonate structures, and show a monotonically decreasing trend with successive CO2 ligand addition. The infrared photodissociation spectra of target ion-molecule complexes were recorded in the 2100-2500 cm-1 frequency region and interpreted by comparison with simulated IR spectra of low-lying isomers representing distinct configurations, demonstrating a high possibility of carbonate structure formation in current experiments.