The roles of bacteria and viruses in COPD-Bronchiectasis association: A prospective cohort study.

BACKGROUND: Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association with exacerbations and clinical outcomes of CBA as compared with bronchiectasis. METHODS: We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations. RESULTS: We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P = 0.02), but not at AE onset (P = 0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8 % vs 32.1 %, P = 0.001) and CBA (19.5 % vs 30.6 %, P = 0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa (PA) correlated with higher modified Reiff score (P = 0.032) in CBA but not in BO (P = 0.178). Repeated detection of PA yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P = 0.006] but not in BO (median: 8.4 vs 7.6 months, P = 0.47). CONCLUSIONS: Isolation of any viruses, human metapneumovirus and bacterialplus viruses was associated with CBA exacerbations. Repeated detection of PA confers greater impact of future exacerbations on CBA than on BO.

Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

Diagnosis of Nonalcoholic Fatty Liver Disease via a H2S-Responsive Bioluminescent Probe Combined with Firefly Luciferase mRNA Delivery.

The early detection of nonalcoholic fatty liver disease (NAFLD) through bioluminescent probes is of great significance. However, there remains a challenge to apply them in nontransgenic natural animals due to the lack of exogenous luciferase. To address this issue, we herein report a new strategy for in situ monitoring of endogenous hydrogen sulfide (H2S) in the liver of NAFLD mice by leveraging a H2S-responsive bioluminescent probe (H-Luc) combined with firefly luciferase (fLuc) mRNA delivery. The probe H-Luc was created by installing a H2S recognition moiety, 2,4-dinitrophenol, onto the luciferase substrate (d-luciferin), which is allowed to release cage-free d-luciferin in the presence of H2S via a nucleophilic aromatic substitution reaction. In the meantime, the intracellular luciferase was introduced by lipid nanoparticle (LNP)-mediated fLuc mRNA delivery, rendering it suitable for bioluminescence (BL) imaging in vitro and in vivo. Based on this luciferase-luciferin system, the endogenous H2S could be sensitively and selectively detected in living cells, showing a low limit of detection (LOD) value of 0.72 µM. More importantly, after systematic administration of fLuc mRNA-loaded LNPs in vivo, H-Luc was able to successfully monitor the endogenous H2S levels in the NAFLD mouse model for the first time, displaying a 28-fold higher bioluminescence intensity than that in the liver of normal mice. We believe that this strategy may shed new light on the diagnosis of inflammatory liver disease, further elucidating the roles of H2S.

Visualization of Endogenous Hypochlorite in Drug-Induced Liver Injury Mice via a Bioluminescent Probe Combined with Firefly Luciferase mRNA-Loaded Lipid Nanoparticles.

Drug-induced liver injury (DILI) is a common liver disease with a high rate of morbidity, and its pathogenesis is closely associated with the overproduction of highly reactive hypochlorite (ClO-) in the liver. However, bioluminescence imaging of endogenous hypochlorite in nontransgenic natural mice remains challenging. Herein, to address this issue, we report a strategy for imaging ClO- in living cells and DILI mice by harnessing a bioluminescent probe formylhydrazine luciferin (ClO-Luc) combined with firefly luciferase (fLuc) mRNA-loaded lipid nanoparticles (LNPs). LNPs could efficiently deliver fLuc mRNA into living cells and in vivo, expressing abundant luciferase in the cytoplasm in situ. In the presence of ClO-, probe ClO-Luc locked by formylhydrazine could release cage-free d-luciferin through oxidation and follow-up hydrolysis reactions, further allowing for bioluminescence imaging. Moreover, based on the luciferase-luciferin system, it was able to sensitively and selectively detect ClO- in vitro with a limit of detection of 0.59 µM and successfully monitor the endogenous hypochlorite generation in the DILI mouse model for the first time. We postulate that this work provides a new method to elucidate the roles of ClO- in related diseases via bioluminescence imaging.

How robot-assisted gait training affects gait ability, balance and kinematic parameters after stroke: a systematic review and meta-analysis.

INTRODUCTION: Gait ability is often cited by stroke survivors. Robot-assisted gait training (RAGT) can help stroke patients with lower limb motor impairment regain motor coordination. EVIDENCE ACQUISITION: PubMed, Cochrane Library, Embase were systematically searched until September 2023, to identify randomized controlled trials presenting: stroke survivors as participants; RAGT as intervention; conventional rehabilitation as a comparator; gait assessment, through scales or quantitative parameters, as outcome measures. EVIDENCE SYNTHESIS: Twenty-seven publications involving 1167 patients met the inclusion criteria. Meta-analysis showed no significant differences in speed, cadence, spatial symmetry, and changes in joint mobility angles between the RAGT group and the control group. In addition, RAGT was associated with changes in affected side step length (SMD=0.02, 95% CI: 0.01, 0.03; P<0.0001), temporal symmetry (SMD=-0.38, 95% CI: -0.6, -0.16; P=0.0006], Six-Minute Walk Test (SMD=25.14, 95% CI: 10.19, 40.09; P=0.0010] and Functional Ambulation Categories (SMD=0.32, 95% CI: 0.01, 0.63; P=0.04). According to the PEDro scale, 19 (70.4%) studies were of high quality and eight were of moderate quality (29.6%). CONCLUSIONS: Taken together, the review synthesis showed that RAGT might have a potential role in the recovery of walking dysfunction after stroke. However, its superiority over conventional rehabilitation requires further research. Additionally, it may provide unexpected benefits that the effects of RAGT with different types or treatment protocols were further compared.

Evaluation of heavy metal speciation distribution in soil and the accumulation characteristics in wild plants: A study on naturally aged abandoned farmland adjacent to tailings.

Heavy metal composite pollution is widespread in the surrounding environment of tailings ponds in arid and semi-arid regions, leading to the abandonment of substantial agricultural land. This study investigates the speciation distribution and plant accumulation characteristics of heavy metals in abandoned farmland with different durations of natural aging. The aim is to comprehend the local heavy metal behavior pattern in the soil-plant system and offer insights for environmental remediation. Our findings reveal that Cd stands out as the primary heavy metal pollutant in this area. The mobility ranking of heavy metals is Cd > Pb > Zn > Cu, with Cd and Pb mobility decreasing along the basin. Notably, active Pb exhibits a higher affinity for soil binding compared to other metals. The predominant plant species in the region are primarily small shrubs, herbaceous plants, and semi-shrubs that demonstrate tolerance to drought and salt. Most plant samples showed elevated levels of Cd, Pb, and Zn, surpassing the maximum tolerance levels for dietary minerals in livestock. This elevated metal content poses potential threats to the health of local livestock and wildlife, yet it is also considered a potential for phytoremediation. Selected dominant plant species from the current study include Kalidium foliatum & gracile which shows potential as a Cd accumulator and indicator. Neotrinia splendens and Reaumuria songarica demonstrate potential as Cd excluders, with the latter exhibiting higher tolerance to Cd (62.9 mg/kg). Additionally, our observations indicate that different plant parts exhibit distinct responses to heavy metals, and Zn synergistically influences the aerial part accumulation of Cd. This study holds significant importance in understanding the complex behavior patterns of multi-metal pollutants in the natural environment. The identification of native plants with remediation potential is valuable for phytoremediation of environment pollution in mining area.

Long-term biogas slurry application increases microbial necromass but not plant lignin contribution to soil organic carbon in paddy soils as regulated by fungal community.

Biogas slurry (BS) is widely considered as a source of organic matter and nutrients for improving soil organic carbon (SOC) sequestration and crop production in agroecosystems. Microbial necromass C (MNC) is considered one of the major precursors of SOC sequestration, which is regulated by soil microbial anabolism and catabolism. However, the microbial mechanisms through which BS application increases SOC accumulation in paddy soils have not yet been elucidated. A 12-year field experiment with four treatments (CK, no fertilizers; CF, chemical fertilizer application; BS1 and BS2, biogas slurry application at two nitrogen rates from BS) was conducted in rice paddy fields. The results showed that long-term BS application had no effect on lignin phenols proportion in SOC relative to CF. In contrast, BS application elevated the MNC contribution to SOC by 15.5-20.5 % compared with the CF treatment. The proportion of fungal necromass C (FNC) to SOC increased by 16.0 % under BS1 and by 25.8 % under BS2 compared with the CF treatment, while no significant difference in bacterial necromass C (BNC) contribution to SOC was observed between the BS and CF treatments. The MNC was more closely correlated with fungal community structures than with bacterial community structures. We further found that fungal genera, Mortierella and Ciliophora, mainly regulated the MNC, FNC and BNC accumulation. Collectively, our results highlighted that fungi play a vital role in SOC storage in paddy soils by regulating MNC formation and accumulation under long-term BS application.

Deep immunoglobulin repertoire sequencing depicts a comprehensive atlas of spike-specific antibody lineages shared among COVID-19 convalescents.

Neutralizing antibodies are a key component in protective humoral immunity against SARS-CoV-2. Currently, available technologies cannot track epitope-specific antibodies in global antibody repertoires. Thus, the comprehensive repertoire of spike-specific neutralizing antibodies elicited by SARS-CoV-2 infection is not fully understood. We therefore combined high-throughput immunoglobulin heavy chain (IgH) repertoire sequencing, and structural and bioinformatics analysis to establish an antibodyomics pipeline, which enables tracking spike-specific antibody lineages that target certain neutralizing epitopes. We mapped the neutralizing epitopes on the spike and determined the epitope-preferential antibody lineages. This analysis also revealed numerous overlaps between immunodominant neutralizing antibody-binding sites and mutation hotspots on spikes as observed so far in SARS-CoV-2 variants. By clustering 2677 spike-specific antibodies with 360 million IgH sequences that we sequenced, a total of 329 shared spike-specific antibody clonotypes were identified from 33 COVID-19 convalescents and 24 SARS-CoV-2-naïve individuals. Epitope mapping showed that the shared antibody responses target not only neutralizing epitopes on RBD and NTD but also non-neutralizing epitopes on S2. The immunodominance of neutralizing antibody response is determined by the occurrence of specific precursors in human naïve B-cell repertoires. We identified that only 28 out of the 329 shared spike-specific antibody clonotypes persisted for at least 12 months. Among them, long-lived IGHV3-53 antibodies are likely to evolve cross-reactivity to Omicron variants through accumulating somatic hypermutations. Altogether, we created a comprehensive atlas of spike-targeting antibody lineages in COVID-19 convalescents and antibody precursors in human naïve B cell repertoires, providing a valuable reference for future vaccine design and evaluation.

Response of trace elements in urban deposition to emissions in a northwestern river valley type city: 2010-2021.

Anthropogenic activities release significant quantities of trace elements into the atmosphere, which can infiltrate ecosystems through both wet and dry deposition, resulting in ecological harm. Although the current study focuses on the emission inventory and deposition of trace elements, their complex interactions remain insufficiently explored. In this study, we employ emission inventories and deposition data for eight TEs (Cr, Mn, Ni, Cu, Zn, As, Cd, Pb) in Lanzhou City to unveil the relationship between these two aspects. Emissions in Lanzhou can be roughly divided into two periods centered around 2017. Preceding 2017, industrial production constituted the primary source of TEs emissions except for As; coal combustion was the primary contributor to Cr, Mn, and As emissions; waste incineration played a significant role in As, Zn, and Cd emissions; biomass combustion influenced Cr and Cd emissions; and transportation sources were the predominant contributors to Pb and Cu emissions. With the establishment of waste-to-energy plants and the implementation of ultra-low emission retrofits, emissions from these sources decreased substantially after 2017. Consequently, emissions from industrial production emerged as the main source of TEs. The deposition concentrations of Cr, Mn, Ni, Cu, and Pb followed a similar trend to the emissions. However, Cd and As exhibited lower emissions and a less pronounced response relationship. Moreover, Zn concentrations fluctuated within a narrow range and showed a weaker response to emissions. The consistent changes in emissions and TEs deposition concentrations signify a shift in deposition pollution in Lanzhou city from Coal-fired pollution to that driven by transportation and industrial activities. Within this transition, the industrial production process offers significant potential for emission reduction. This insight provides a crucial foundation for managing TEs pollution and implementing strategies to prevent ecological risks.

Assessment and machine learning prediction of heavy metals fate in mining farmland assisted by Positive Matrix Factorization.

The accurate pollutant prediction by Machine Learning (ML) is significant to efficient environmental monitoring and risk assessment. However, application of ML in soil is under studied. In this study, a Positive Matrix Factorization (PMF) assisted prediction method was developed with Support Vector Machine (SVM) and Random Forest (RF) for heavy metals (HMs) prediction in mining farmland. Principal Component Analysis (PCA) and Redundancy Analysis (RDA) were selected to pretreat data. Experiment results illustrated Cd was the main pollutant with heavy risks in the study area and Pb was easy to migrate. The method effects of HMs total concentration predicting were PMF > Simple > PCA > PCA - PMF, and RF predicted better than SVM. Data pretreatment by RDA prior inspection improved the model results. Characteristic HMs Tessier fractions prediction received good effects with average R value as 0.86. Risk classification prediction performed good in Cd, Cu, Ni and Zn, however, Pb showed weak effect by simple model. The best classifier method for Pb was PMF - RF method with relatively good effect (Area under ROC Curve = 0.896). Overall, our study suggested the combination between PMF and ML can assist the prediction of HMs in soil. Spatial weighted attribute of HMs can be provided by PMF.

Modular Design of Biodegradable Ionizable Lipids for Improved mRNA Delivery and Precise Cancer Metastasis Delineation In Vivo.

Lipid nanoparticles (LNPs) represent the most clinically advanced nonviral mRNA delivery vehicles; however, the full potential of the LNP platform is greatly hampered by inadequate endosomal escape capability. Herein, we rationally introduce a disulfide bond-bridged ester linker to modularly synthesize a library of 96 linker-degradable ionizable lipids (LDILs) for improved mRNA delivery in vivo. The top-performing LDILs are composed of one 4A3 amino headgroup, four disulfide bond-bridged linkers, and four 10-carbon tail chains, whose unique GSH-responsive cone-shaped architectures endow optimized 4A3-SCC-10 and 4A3-SCC-PH lipids with superior endosomal escape and rapid mRNA release abilities, outperforming their parent lipids 4A3-SC-10/PH without a disulfide bond and control lipids 4A3-SSC-10/PH with a disulfide bond in the tail. Notably, compared to DLin-MC3-DMA via systematic administration, 4A3-SCC-10- and 4A3-SCC-PH-formulated LNPs significantly improved mRNA delivery in livers by 87-fold and 176-fold, respectively. Moreover, 4A3-SCC-PH LNPs enabled the highly efficient gene editing of 99% hepatocytes at a low Cre mRNA dose in tdTomato mice following intravenous administration. Meanwhile, 4A3-SCC-PH LNPs were able to selectively deliver firefly luciferase mRNA and facilitate luciferase expression in tumor cells after intraperitoneal injection, further improving cancer metastasis delineation and surgery via bioluminescence imaging. We envision that the chemistry adopted here can be further extended to develop new biodegradable ionizable lipids for broad applications such as gene editing and cancer immunotherapy.

Advances on micro/nanoplastics and their effects on the living organisms: A review.

Micro/nanoplastics (MPs) are attracting increasing attention owing to the potential threats they pose to the sustainability of the environment and the health of living organisms. Thus, a comprehensive understanding of the influence of MPs on living organisms is vital for developing countermeasures. We conducted an extensive literature search to retrieve the articles related to MPs via the Web of Science. Accordingly, 152 articles published in the last decade and in influential journals were selected to analyze the effects of MPs on plants, animals, microorganisms, and humans as well as the current status, hotspots, and trends of studies on MPs. The results showed that owing to the special characteristics of MPs and anthropogenic activities, MPs have become ubiquitous worldwide. MPs are ingested by plants and animals and enter the human body through various pathways, resulting in numerous adverse effects, such as growth inhibition, oxidative stress, inflammation, organ damage, and germ cell lesions. Moreover, they affect microorganisms by reshaping the structure and function of microbial communities and changing the spread pathway. However, microorganisms can also contribute to the degradation of MPs. With increasing evidence of the adverse effects of MPs on biota, coping with MP pollution and mitigating harmful outcomes have emerged as major challenges. This review focuses on (1) the main effects of MPs on living organisms, ranging from microorganisms to humans, (2) the current status and hotspots of studies related to MPs, and (3) the challenges and prospects of further studies on MPs.

"Dual-Key-and-Lock" NIR-II NSCyanines Enable High-Contrast Activatable Phototheranostics in Extrahepatic Diseases.

Conventional cyanine dyes with a symmetric structure are "always-on", which can easily accumulate in the liver and display high liver background fluorescence, inevitably interfering the accurate diagnosis and therapy in extrahepatic diseases. We herein report a platform of NIR-II non-symmetric cyanine (NSCyanine) dyes by harnessing a non-symmetric strategy, which are extremely sensitive to pH/viscosity and can be activated via a "dual-key-and-lock" strategy. These NSCyanine dyes with a low pKa (<4.0) only show weak fluorescence at lysosome pH (key1), however, the fluorescence can be completely switched on and significantly enhanced by intracellular viscosity (key2) in disease tissues, exhibiting high target-to-liver ratios up to 19.5/1. Notably, high-contrast phototheranostics in extrahepatic diseases are achieved, including intestinal metastasis-imaging, acute gastritis-imaging, bacteria infected wound healing, and tumor ablation via targeted combined photothermal therapy and chemotherapy.

Dynamic characteristics of heavy metal accumulation in agricultural soils after continuous organic fertilizer application: Field-scale monitoring.

Manure has been considered as a source of soil heavy metal (HM) pollution. However, the long-term impact of manure application on soil HM accumulation have not been well studied. This study tracked the long-term cumulative trends of soil copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) in three soil-crop systems over 5-8 years' application of commercial manure fertilizer. The contribution of different fertilization treatments (CF, chemical fertilizer; T1-T3, manure with different application dosages) to soil HMs pollution risk were assessed. There are accumulating tendencies for Cu, Zn, and Pb in paddy fields, Cu and As in orchard fields, and Zn, As, and Pb in vegetable fields, while the concentrations of As in paddy fields and Zn in orchard fields decreased over time. Manure application significantly influenced the accumulation of Cu, Zn, and As in soils rather than that of Pb. The modeling prediction subsequently revealed that the time required to reach the risk screening values (Cu: 50 mg kg-1; Zn: 200 mg kg-1) for HM content in paddy soil, according to GB15618-2018, decreased from 18.20 years to 7.20 years due to the introduction of Cu and Zn via manure use. Recommend annual manure application dosage was 7.73 t hm-2 y-1 to ensure a 20-year period of clean production in paddy soils, while it was 26.15 t hm-2 y-1 in the orchard soil and 16.23 t hm-2 y-1 in vegetable soil to ensure a 50-year period of clean production, respectively. Overall, the impacts of HMs input by manure application on soil HMs accumulation varied depending on the type of metal and the soil-crop system. The cumulative trends of HMs in soils play a crucial role in determining whether the input of HMs through manure application can lead to the risk of HM pollution.

Advances in pharmacotherapy for bronchiectasis in adults.

INTRODUCTION: Bronchiectasis has become a growing concern of chronic airway disease because of the enormous socioeconomic burden. Four cardinal interdependent components - impaired airway defense, recurrent airway infections, inflammatory response, and airway damage, in conjunction with the underlying etiology, have collectively played a role in modulating the vicious vortex of the pathogenesis and progression of bronchiectasis. Current pharmacotherapy aims to target at these aspects to break the vicious vortex. AREAS COVERED: The authors retrieve and review, in MEDLINE, Web of Science and ClinicalTrials.gov registry, the studies about pharmacotherapy for bronchiectasis from these aspects: antibiotics, mucoactive medications, bronchodilators, anti-inflammatory drug, and etiological treatment. EXPERT OPINION: Future drug development and clinical trials of bronchiectasis need to pay more attention to the different phenotypes or endotypes of bronchiectasis. There is a need for the development of novel inhaled antibiotics that could reduce bacterial loads, improve quality-of-life, and decrease exacerbation risks. More efforts are needed to explore the next-generation neutrophil-targeted therapeutic drugs that are expected to ameliorate respiratory symptom burden, reduce exacerbation risks, and hinder airway destruction in bronchiectasis.

Source identification and health risk assessment of heavy metals with mineralogy: the case of soils from a Chinese industrial and mining city.

Understanding the precise sources of heavy metals (HMs) in soil and the contribution of these sources to health risks has positive effects in terms of risk management. This study focused on the HMs in the soil of five land uses in an industrial and mining city. The sources of HMs in soils were identified, and the soil mineralogical characteristics and health risks of HMs were discussed. The results showed that the HMs (Cu, Zn, Ni, Cd, Pb) found in the soil of the five land uses were affected by human activities. For example, the Cu in grassland, gobi beach, woodland, green belt, and farmland is 22.3, 3.5, 22.5, 16.7, and 21.3 times higher than the soil background values in Gansu Province, respectively. The Positive Matrix Factorization model (PMF) results revealed that traffic emissions and industrial and agricultural activities were the primary sources of HMs in the soil, with industrial sources accounting for the largest share at 55.79%. Furthermore, various characteristics proved that the studied HMs were closely related to smelting products. Concentration-oriented health risk assessments showed that HMs in the different soil types held non-carcinogenic and carcinogenic risks for children and adults. Contamination source-oriented health risk assessments of children and adults found that industrial activities controlled non-carcinogenic and carcinogenic risks. This study highlighted the critical effects of smelting on urban soil and the contribution of pollution sources to health risks. Furthermore, this work is significant in respect of the risk control of HMs in urban soils.

Sources, transfers and the fate of heavy metals in soil-wheat systems: The case of lead (Pb)/zinc (Zn) smelting region.

Heavy metals (HMs) from smelters pose severe challenges to the environmental soil quality of surrounding farmlands, and threaten human health through the food chain. This study explored the environmental effects of smelting activities on farmland soil, and additionally assessed the enrichment, transfer and health risk of HMs in soil-wheat systems. Multiple characterization results were combined to demonstrate that HMs from smelter waste were transferred to the surrounding soil. It was determined that the enrichment of HMs in soil-wheat systems is mainly controlled by the total HM concentration and pH in soil. Furthermore, the priority pollutant in soil-wheat systems was found to be Cd, and Cd affected the transfer of Cu, Mn and Pb from soil to wheat roots. Interestingly, the -OH stretching, C-H stretching, N-H amide and C-O bending were involved in detoxifying HMs in wheat. The mean values of non-carcinogenic and carcinogenic risks by consuming wheat grain were 9.1, 1.4E-02 (adults) and 11.3, 3.3E-03 (children), respectively, indicating a noteworthy health risk. This study highlighted the critical issues arising from Pb/Zn smelting activities on agricultural soils. Notwithstanding, to ensure food security, the affected regions could opt to follow up on the type of crops grown.

Endothelial miR-196b-5p regulates angiogenesis via the hypoxia/miR-196b-5p/HMGA2/HIF1α loop.

Angiogenesis is involved in development, reproduction, wound healing, homeostasis, and other pathophysiological events. Imbalanced angiogenesis predisposes patients to various pathological processes, such as angiocardiopathy, inflammation, and tumorigenesis. MicroRNAs (miRNAs) have been found to be important in regulating cellular processing and physiological events including angiogenesis. However, the role of miRNAs that regulate angiogenesis (angiomiRs) is not fully understood. Here, we observed a downregulation of the miR-196 family in endothelial cells upon hypoxia. Functionally, miR-196b-5p inhibited the angiogenic functions of endothelial cells in vitro and suppressed angiogenesis in Matrigel plugs and skin wound healing in vivo. Mechanistically, miR-196b-5p bound onto the 3' untranslated region (UTR) of high-mobility group AT-hook 2 (HMGA2) mRNA and repressed the translation of HMGA2, which in turn represses HIF1α accumulation in endothelial cells upon hypoxia. Together, our results establish the role of endothelial miR-196b-5p as an angiomiR that negatively regulates endothelial growth in angiogenesis via the hypoxia/miR-196b-5p/HMGA2/HIF1α loop. miR-196b-5p and its regulatory loop could be an important addition to the molecular mechanisms underlying angiogenesis and may serve as potential targets for antiangiogenic therapy.

Effect of Electroacupuncture Added to Pelvic Floor Muscle Training in Women with Stress Urinary Incontinence: A Randomized Clinical Trial.

BACKGROUND: Pelvic floor muscle training (PFMT) is a first-line conservative therapy for stress urinary incontinence (SUI). Electroacupuncture (EA) has been used to treat SUI recently. OBJECTIVE: To compare the effectiveness of PFMT + EA versus PFMT + sham EA for SUI in women. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, randomized, controlled clinical trial was conducted at four hospitals in China involving 304 women with SUI from May 20, 2014 to November 21, 2017. Data were analyzed from April 20 to December 21, 2018. INTERVENTION: Participants were randomized to receive 8 wk of PFMT+ EA (n = 154) or PFMT + sham EA (n = 150). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the change in the amount of urine leakage measured on a 1-hr pad test. Student's t test, the χ2 test, and the Wilcoxon rank-sum test were used for data analysis. RESULTS AND LIMITATIONS: Among the 304 participants randomized, 286 completed the study. The mean age was 57.6 yr (standard deviation [SD] 8.9) for the PFMT + sham EA group and 57.2 yr (SD 9.1) for the PFMT + EA group. The mean urine leakage at baseline was 13.6 g for the PFMT + sham EA group and 13.9 g for the PFMT + EA group. After the 8-wk intervention, the PFMT + EA group had a greater decrease in mean urine leakage (-9.8 g) than the PFMT + sham EA group (-5.8 g) with a mean difference of 4.0 g (95% confidence interval [CI] 0.8-7.2). Significantly more patients experienced a ≥50% reduction in urine leakage and the mean number of incontinence episodes in 24 h in the PFMT + EA group than in the PFMT + sham EA group (26.3%, 95%CI 15.8-36.8%). The PFMT + EA group experienced better improvement in participant-reported SUI severity at 6 wk (p < 0.001) and 8 wk (p < 0.001) and self-evaluated therapeutic effects at 2-32 wk (p < 0.001) after the intervention. Lack of measurement of the amount of urine leakage during follow-up is a limitation. CONCLUSIONS: In this randomized clinical trial, 8-wk combined treatment with PFMT + EA led to a greater improvement in SUI symptoms and better outcomes than with PFMT + sham EA. PATIENT SUMMARY: We evaluated the effectiveness and safety of pelvic floor muscle training combined with electroacupuncture for stress urinary incontinence in women, Our results show that this is a promising therapeutic approach for the treatment of stress urinary incontinence.

Molecularly imprinted self-buffering double network hydrogel containing bi-amidoxime functional groups for the rapid hydrolysis of organophosphates.

The development of high-performance catalyst materials with high catalytic activity for the hydrolysis of organophosphorus toxicants without additional pH buffer conditions has become an urgent need for practical application. Here, a multifunctional molecularly imprinted polymer double network hydrogel (MIP-DN) material has been prepared by integrating the first polymer network containing the functional group of bi-amidoxime as the catalytic active center and the cationic polymer polyethyleneimine (PEI) with pH buffer function as the main component of the second network. Advantageously, the resultant MIP-DN hydrogel showed excellent catalytic performance without additional pH buffer conditions, exhibiting a half-life of 25 min for the hydrolysis of paraoxon in pure water. Together with multi-functions of high catalytic activity, self-buffering function and excellent processability, the MIP-DN hydrogel prepared in this work provides a new strategy for the preparation of catalytic materials with practical application value toward toxic organophosphates.