Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Grain boundary defect engineering in rutile iridium oxide boosts efficient and stable acidic water oxidation.

PEMWE is considered a promising technology for coupling with renewable energy sources to achieve clean hydrogen production. However, constrained by the sluggish kinetics of the anodic OER and the acidic abominable environment render the grand challenges in developing the active and stable OER electrocatalyst, leading to low efficiency of PEMWE. Herein, we develop the rutile-type IrO2 nanoparticles with abundant grain boundaries and the continuous nanostructure through the joule heating and sacrificial template method. DFT calculations verified that grain boundaries can modulate the electronic structure of Ir sites and optimize the adsorption of oxygen intermediates, resulting in the accelerated kinetics. The 350-IrO2 affords a rapid OER process with 20 times higher mass activity (0.61 A mgIr-1) than the commercial IrO2 at 1.50 V vs. RHE. Benefiting from the reduced overpotential and the preservation of the stable rutile structure, 350-IrO2 exhibits the stability of 200 h test at 10 mA cm-2 with only trace decay of 11.8 mV. Moreover, the assembled PEMWE with anode 350-IrO2 catalyst outputs the current density up to 2 A cm-2 with only 1.84 V applied voltage, long-term operation for 100 h without obvious performance degradation at 1 A cm-2.

The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

[Clinical value of high frequency ultrasound in the diagnosis of hip joint involvement in patients with ankylosing spondylitis].

OBJECTIVE: To analyze the correlation between hip joint musculoskeletal ultrasound score and ankylosing spondylitis (AS) disease activity, as well as to investigate the value of high frequency ultrasound in the assessment of hip joint involvement in AS. METHODS: The clinical data of 244 patients with AS who were treated in the rheumatology department of from March 2019 to March 2022 were retrospectively analyzed. Among them, there 174 males and 70 females, aged from 19 to 58 years old with an average of (34.22±9.49) years old;the disease duration of AS patients ranged from 8 months to 26 years, with an average of (13.68±4.04) years.The 244 patients were divided into disease group (83 cases) and control group (161 cases) based in the presence of hip joint involuement. According to the the disease activity, patients in the disease group were further categorezed into active phase (45 cases) and stable phase (38 cases). The ultrasound scores of patients in the active and stable phases of the disease group and the control group were compared. Relevant factors of hip joint involvement in AS patients were analyzed, and analyze the correlation between ultrasound score and Bath ankylosing spondylitis disease activity score index(BASDAI), Bath ankylosing spondylitis functional index(BASFI), visual analogue score of pain (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the correlation between hip joint capsule score and tendon attachment end score and BASDAI, BASFI, VAS, CRP and ESR. RESULTS: The hip joint capsule score(3.06±1.12), femoral head score(1.45±0.43), tendon attachment end score(3.28±1.30) and total ultrasound score(6.65±2.31) of the disease group were higher than those of the control group(1.51±0.48)、(0.66±0.27)、(1.61±0.53)、(3.81±1.44)scores (P<0.05). Multifactor Logstic regression analysis showed that the course of disease, hip joint capsule score and total ultrasound score were independent risk factors for hip involvement in AS patients.The hip capsule score (3.65±1.22)and total ultrasound score(8.28±2.33) in the active phase of the disease group were higher than those in the stable phase (2.48±1.04)、( 6.82±1.96)scores(P<0.05). The hip joint capsule score and total ultrasonic score of AS patients were positively correlated with BASDAI, BASFI, VAS, CRP, and ESR (P<0.05, P<0.01).The score of tendon attachment end was positively correlated with CRP (P<0.05). The score of joint capsule effusion in AS patients was positively correlated with BASDAI, BASFI and VAS (P<0.05, P<0.01). The synovial blood flow score was positively correlated with BASDAI, VAS, CRP and ESR (P<0.05, P<0.01). The synovial thickening score was positively correlated with BASDAI, BASFI, VAS, CRP and ESR (P<0.05, P<0.01). There was no correlation between the score of tendon attachment end and BASDAI, BASFI, VAS, CRP and ESR. CONCLUSION: There is a correlation between hip joint ultrasonic score of hip joint and clinical indexes in AS patients.Hip joint capsule score and total ultrasonic score were independent risk factors for hip involvement in AS patients. High frequency ultrasound exhibits clinical value in the diagnosis of hip joint involvement in AS patients.

Outdoor gardening activity with different frequency and duration may be associated with reduction of total and cause-specific mortality risk for general U.S. adults: Findings from the NHANES.

BACKGROUND AND AIMS: Engaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. METHODS AND RESULTS: A total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8-18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. CONCLUSION: Our study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.

Chronic myeloid leukaemia: Biology and therapy.

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions.

Cumulative inequality in social determinants of health in relation to depression symptom: An analysis of nationwide cross-sectional data from U.S. NHANES 2005-2018.

Social determinants of health (SDoH) have been linked to a higher likelihood of experiencing mental health problems. This study aimed to investigate whether the accumulation of unfavorable SDoH is associated with depression symptom. Data was gathered from a representative population participating in the U.S. National Health and Nutrition Examination Survey spanning from 2005 to 2018. Self-reported SDoH were operationalized according to the criteria outlined in Healthy People 2030, with a cumulative measure of unfavorable SDoH calculated for analysis. The presence of depression symptom was identified using the Patient Health Questionnaire in a representative sample of 30,762 participants (49.2 % males) representing 1,392 million non-institutionalized U.S. adults, with 2,675 (8.7 %) participants showing depression symptom. Unfavorable SDoH were found to be significantly and independently associated with depression symptom. Individuals facing multiple unfavorable SDoHs were more likely to experience depression symptom (P for trend < 0.001). For instance, a positive association was observed in participants exposed to six or more unfavorable SDoHs with depression symptom (AOR = 3.537, 95 % CI: 1.781, 7.075, P-value < 0.001). The findings emphasize that the likelihood of developing depression symptom significantly increases when multiple SDoHs are present, compared to just a single SDoH.

Source-specified atmospheric age distribution of black carbon and its impact on optical properties over the Yangtze River Delta.

Black carbon (BC) exerts a profound and intricate impact on both air quality and climate due to its high light absorption. However, the uncertainty in representing the absorption enhancement of BC in climate models leads to an increased range in the modeled aerosol climate effects. Changes in BC optical properties could result either from atmospheric aging processes or from variations in its sources. In this study, a source-age model for identifying emission sources and aging states presented by University of California at Davis/California Institute of Technology (UCD/CIT) was used to simulate the atmospheric age distribution of BC from different sources and to quantify its impact on the optical properties of BC-containing particles. The results indicate that regions with greater aged BC concentrations do not correspond to regions with higher BC emissions due to atmospheric transport. High concentrations of aged BC are found in northern Yangtze River Delta (YRD) regions during summer. The chemical compositions of particles from different sources and with different atmospheric ages differ significantly. BC and primary organic aerosols (POA) are dominating in Traffic-dominated source while other components dominate in Industry-dominated source. As the atmospheric age increases, the mass fraction of secondary inorganic aerosols rises. Compared to the original model, the simulated mass absorption cross section of BC particles in the source-age model decreases while the single scattering albedo increases. This compensates for ~11 % of the overestimation of the simulated BC direct radiative forcing. Our study highlights that incorporating atmospheric age and source information into models can greatly improve the estimation of optical properties of BC-containing particles and deepen our understanding of their climate effects.

Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor.

The chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

Quantifying the Chemical Composition and Real-Time Mass Loading of Nanoplastic Particles in the Atmosphere Using Aerosol Mass Spectrometry.

Plastic debris, including nanoplastic particles (NPPs), has emerged as an important global environmental issue due to its detrimental effects on human health, ecosystems, and climate. Atmospheric processes play an important role in the transportation and fate of plastic particles in the environment. In this study, a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS) was employed to establish the first online approach for identification and quantification of airborne submicrometer polystyrene (PS) NPPs from laboratory-generated and ambient aerosols. The fragmentation ion C8H8+ is identified as the major tracer ion for PS nanoplastic particles, achieving an 1-h detection limit of 4.96 ng/m3. Ambient PS NPPs measured at an urban location in Texas are quantified to be 30 ± 20 ng/m3 by applying the AMS data with a constrained positive matrix factorization (PMF) method using the multilinear engine (ME-2). Careful analysis of ambient data reveals that atmospheric PS NPPs were enhanced as air mass passed through a waste incinerator plant, suggesting that incineration of waste may serve as a source of ambient NPPs. The online quantification of NPPs achieved through this study can significantly improve our understanding of the source, transport, fate, and climate effects of atmospheric NPPs to mitigate this emerging global environmental issue.

Broadening oncological boundaries: the intratumoral microbiota.

The microbiota of solid tumors was identified >100 years ago; however, heterogeneous composition and diversity have been revealed only recently. Growing evidence has suggested that several functional mechanisms of the intratumoral microbiota affect tumorigenesis and progression, suggesting that the intratumoral microbiota is a promising biomarker for multiple cancers. The low biomass of the intratumoral microbiota poses a major challenge to related research, thus necessitating the use of a multiple-modality integrated framework to resolve this dilemma. Advanced techniques such as single-cell sequencing provide significant clues, and the gradual optimization of functional experiments and culture-based methods enables deeper investigation of the underlying mechanisms involved. In this review, we outline the current state of research on the intratumoral microbiota and describe the challenges and comprehensive strategies for future research.

Genome-wide identification and expression analysis of NIN-like protein (NLP) genes: Exploring their potential roles in nitrate response in tea plant (Camellia sinensis).

NIN-like proteins (NLPs) are evolutionarily conserved transcription factors that are unique to plants and play a pivotal role in responses to nitrate uptake and assimilation. However, a comprehensive analysis of NLP members in tea plants is lacking. The present study performed a genome-wide analysis and identified 33 NLP gene family members of Camellia sinensis that were distributed unequally across 5 chromosomes. Subcellular localisation predictions revealed that all CsNLP proteins were localised in the nucleus. Conservative domain analysis revealed that all of these proteins contained conserved RWP-RK and PB1 domains. Phylogenetic analysis grouped the CsNLP gene family into four clusters. The promoter regions of CsNLPs harboured cis-acting elements associated with plant hormones and abiotic stress responses. Expression profile analysis demonstrated that CsNLP8 was significantly upregulated in roots under nitrate stress conditions. Subcellular localisation analysis found CsNLP8 localised to the nucleus. Dual-luciferase reporter assay demonstrated that CsNLP8 positively regulated the expression of a nitrate transporter gene (CsNRT2.2). These findings provide a comprehensive characterisation of NLP genes in Camellia sinensis and offer insights into the biological function of CsNLP8 in regulating the response to nitrate-induced stress.

Dominant contribution of combustion-related ammonium during haze pollution in Beijing.

Aerosol ammonium (NH4+), mainly produced from the reactions of ammonia (NH3) with acids in the atmosphere, has significant impacts on air pollution, radiative forcing, and human health. Understanding the source and formation mechanism of NH4+ can provide scientific insights into air quality improvements. However, the sources of NH3 in urban areas are not well understood, and few studies focus on NH3/NH4+ at different heights within the atmospheric boundary layer, which hinders a comprehensive understanding of aerosol NH4+. In this study, we perform both field observation and modeling studies (the Community Multiscale Air Quality, CMAQ) to investigate regional NH3 emission sources and vertically resolved NH4+ formation mechanisms during the winter in Beijing. Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH3 emissions, including fossil fuel sources, NH3 slip, and biomass burning, are important sources of aerosol NH4+ with more than 60% contribution occurring on heavily polluted days. In contrast, volatilization-related NH3 sources (livestock breeding, N-fertilizer application, and human waste) are dominant on clean days. Combustion-related NH3 is mostly local from Beijing, and biomass burning is likely an important NH3 source (∼15%-20%) that was previously overlooked. More effective control strategies such as the two-product (e.g., reducing both SO2 and NH3) control policy should be considered to improve air quality.

Contribution of individual and cumulative social determinants of health underlying gender disparities in periodontitis in a representative US population: A cross-sectional NHANES study.

AIM: To examine the impact of both individual and cumulative social determinants of health (SDoH) on the likelihood of developing periodontitis, while also exploring any gender disparities in this relationship. MATERIALS AND METHODS: Data of self-reported SDoH domains and sub-items based on Healthy People 2030 were obtained from the U.S. National Health and Nutrition Examination Surveys between 1999 and 2014. Logistic regression models, weighted by survey responses, were used to examine the relationship between SDoH (including eight sub-items and the cumulative number of unfavourable SDoH) and periodontitis. The results were further analysed by gender. RESULTS: A total of 18,075 participants (8867 males and 9208 females) were included in the main analysis, of which 5814 (32.2%) had periodontitis. The study found that certain unfavourable SDoH were individually associated with higher odds of periodontitis, and the cumulative number of unfavourable SDoH was positively linked to the odds of developing periodontitis. Furthermore, males exposed to more unfavourable SDoH appeared to be more susceptible to developing periodontitis than females. CONCLUSIONS: The findings suggest that unfavourable SDoH, especially when they accumulate, are associated with an increased odds of periodontitis and contribute to gender disparities within the U.S.

An analysis of different concepts of "identity" in the heritable genome editing debate.

Human heritable genome editing (HHGE) involves editing the genes of human gametes and/or early human embryos. Whilst 'identity' is a key concept underpinning the current HHGE debate, there is a lack of inclusive analysis on different concepts of 'identity' which renders the overall debate confusing at times. This paper first contributes to reviewing the existing literature by consolidating how 'identity' has been discussed in the HHGE debate. Essentially, the discussion will reveal an ontological and empirical understanding of identity when different types of identity are involved. Here, I discuss genetic, numerical, qualitative and narrative and how each of them is relevant in the HHGE context. Secondly, given the different types of identity, the paper explores how we could navigate these different interpretations of identity in a way that promotes an inclusive and informed discussion between primary stakeholders and the general public in the HHGE debate. Here, I argue for and refine a multi-faceted concept of identity as a suitable framework for discussing the ethical and societal implications of HHGE because it not only could integrate different understandings of identity but also highlight the interconnectedness between these different understandings.

Comparison of PM2.5 Air Pollution Exposures and Health Effects Associations Using 11 Different Modeling Approaches in the Women's Health Initiative Memory Study (WHIMS).

BACKGROUND: Many approaches to quantifying air pollution exposures have been developed. However, the impact of choice of approach on air pollution estimates and health-effects associations remains unclear. OBJECTIVES: Our objective is to compare particulate matter with aerodynamic diameter ≤2.5µm (PM2.5) concentrations and resulting health effects associations using multiple estimation approaches previously used in epidemiologic analyses. METHODS: We assigned annual PM2.5 exposure estimates from 1999 to 2004 derived from 11 different approaches to Women's Health Initiative Memory Study (WHIMS) participant addresses within the contiguous US. Approaches included geostatistical interpolation approaches, land-use regression or spatiotemporal models, satellite-derived approaches, air dispersion and chemical transport models, and hybrid models. We used descriptive statistics and plots to assess relative and absolute agreement among exposure estimates and examined the impact of approach on associations between PM2.5 and death due to natural causes, cardiovascular disease (CVD) mortality, and incident CVD events, adjusting for individual-level covariates and climate-based region. RESULTS: With a few exceptions, relative agreement of approach-specific PM2.5 exposure estimates was high for PM2.5 concentrations across the contiguous US. Agreement among approach-specific exposure estimates was stronger near PM2.5 monitors, in certain regions of the country, and in 2004 vs. 1999. Collectively, our results suggest but do not quantify lower agreement at local spatial scales for PM2.5. There was no evidence of large differences in health effects associations with PM2.5 among estimation approaches in analyses adjusted for climate region. CONCLUSIONS: Different estimation approaches produced similar spatial patterns of PM2.5 concentrations across the contiguous US and in areas with dense monitoring data, and PM2.5-health effects associations were similar among estimation approaches. PM2.5 estimates and PM2.5-health effects associations may differ more in samples drawn from smaller areas or areas without substantial monitoring data, or in analyses with finer adjustment for participant location. Our results can inform decisions about PM2.5 estimation approach in epidemiologic studies, as investigators balance concerns about bias, efficiency, and resource allocation. Future work is needed to understand whether these conclusions also apply in the context of other air pollutants of interest. https://doi.org/10.1289/EHP12995.

Synergistic anti-tumor effect of dual drug co-assembled nanoparticles based on ursolic acid and sorafenib.

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.