A longevity level-oriented wellness target area identification method: a case study of Yunnan Province, China.

Background: Aging, as a global demographic issue, is characterized by its rapid growth, which drives an increase in people's healthcare awareness. The emergence of wellness bases caters to this market demand. Therefore, the identification of potential areas suitable for wellness activities and the construction of wellness bases, referred to as Wellness Target Areas (WTAs), becomes a crucial first step. Currently, commonly used identification methods are mostly based on traditional statistical approaches, which are often complex, cumbersome, and subject to potential risks of subjective assumptions, affecting the reliability of WTAs identification results. Longevity level serves as a comprehensive indicator reflecting the natural and socio-economic environment of a region, making it the most indicative of the regional wellness environment status. Methods: This study proposes using longevity level as the benchmark for WTAs identification to simplify the identification process and reduce the impact of subjective bias on the results. The study focuses on 129 county-level units in Yunnan Province. Firstly, the Geodetector (GD) is utilized to explore the complex interaction between the longevity level and the geographical environment to determine regional wellness factors. Secondly, using ArcGIS and geographical weighted regression (GWR), the study investigates the role of different wellness factors, ultimately classifying and grading the WTAs. Results: The longevity level in Yunnan Province exhibits a pattern of multi-point clustering, forming three major longevity regions. Factors that significantly influence longevity level include annual average precipitation, sunshine duration, PM2.5 content, per capita disposable income, density of tourist attractions, and distance from residential areas to hospitals. Based on the degree of longevity and the contribution rate of influencing factors, Yunnan Province's WTAs are classified into three levels and two types (natural and comprehensive). Conclusion: Our study aims to establish a connection between longevity level and the selection of wellness bases, exploring regional wellness factors through the relationship between longevity phenomena and geographical environment, identifying potential construction areas for wellness bases (i.e., WTAs), providing new insights for the precise selection of wellness bases, effectively enhancing the scientificity of site selection, promoting population health, and contributing to the global aging process with better health.

Regional policy options for carbon peaking in the Yangtze River Delta under uncertainty.

The Yangtze River Delta (YRD) region plays a crucial role in achieving China's carbon peaking goal. However, due to uncertainties surrounding future economic growth, energy consumption, energy structure, and population, the attainment of carbon peaking in this region remains uncertain. To address this issue, this study utilized the generalized Divisia index method to analyze the driving factors of carbon emissions, including economy, energy, investment, and population. Subsequently, Monte Carlo simulations were combined with scenario analysis to dynamically explore the peak path of regional heterogeneity in the YRD from 2022 to 2035 under uncertain conditions. The findings highlighted that economic uncertainty has the most significant impact on carbon emissions. Furthermore, reducing energy intensity and promoting the transformation of the energy consumption structure contribute to carbon reduction. The study also revealed that the carbon peak in the YRD exhibits regional heterogeneity. According to the baseline scenario, carbon emissions in the YRD will not peak before 2035. However, under the low-carbon development scenario, the carbon emissions of Zhejiang and Shanghai will peak before 2030. Moreover, under the enhanced emission reduction (EE) scenario, carbon emissions in Jiangsu, Zhejiang, and Shanghai will peak before 2025, while Anhui will reach its peak before 2030. Collectively, the entire YRD region is forecasted to attain a carbon emissions peak of 2.29 billion tons by 2025 under the EE scenario. This study provides valuable insights into the carbon emission trajectories of the YRD region under uncertain conditions. The findings can be instrumental in formulating carbon peaking policies that account for regional heterogeneity.

The methodological quality of systematic reviews regarding the Core Outcome Set (COS) development.

BACKGROUND: The Core Outcome Measures in Effectiveness Trials (COMET) working group proposed core outcome sets (COS) to address the heterogeneity in outcome measures in clinical studies. According to the recommendations of COMET, performing systematic reviews (SRs) usually was the first step for COS development. However, the SRs that serve as a basis for COS are not specifically appraised by organizations such as COMET regarding their quality. Here, we investigated the status of SRs related to development of COS and evaluated their methodological quality. METHODS: We conducted a search on PubMed to identify SRs related to COS development published from inception to May 2022. We qualitatively summarized the disease included in SR topics, and the studies included in the SRs. We evaluated the methodological quality of the SRs using AMSTAR 2.0 and compared the overall quality of SRs with and without protocols using the Mann-Whitney U test. RESULTS: We included 175 SRs from 23 different countries or regions, and they mainly focused on five diseases: musculoskeletal system or connective tissue disease (n = 19, 10.86%), injury, poisoning, or certain other consequences of external causes (n = 18, 10.29%), digestive system disease (n = 16, 9.14%), nervous system disease (n = 15, 8.57%), and genitourinary system disease (n = 15, 8.57%). Although 88.00% of SRs included randomized controlled trials (RCTs), only a few SRs (23.38%) employed appropriate tools to assess the risk of bias in RCTs. The assessment results on the basis of AMSTAR 2.0 indicated that most SRs (93.71%) were rated as ''critically low'' to ''low'' in terms of overall confidence. The overall confidence of SRs with protocols was significantly higher than that without protocols (P <.001). Compared to the SRs with protocols on Core Outcome Measures in Effectiveness Trials (COMET), SRs with protocols on PROSPERO were of better overall confidence (P = .017). CONCLUSION: The overall quality of published SRs regarding COS development was poor. Our findings emphasize the need for researchers to carefully select the disease topic and strictly adhere to the requirements of optimal methodology when conducting a SR for the establishment of a COS.

Efficient identification of QTL for agronomic traits in foxtail millet (Setaria italica) using RTM- and MLM-GWAS.

KEY MESSAGE: Eleven QTLs for agronomic traits were identified by RTM- and MLM-GWAS, putative candidate genes were predicted and two markers for grain weight were developed and validated. Foxtail millet (Setaria italica), the second most cultivated millet crop after pearl millet, is an important grain crop in arid regions. Seven agronomic traits of 408 diverse foxtail millet accessions from 15 provinces in China were evaluated in three environments. They were clustered into two divergent groups based on genotypic data using ADMIXTURE, which was highly consistent with their geographical distribution. Two models for genome-wide association studies (GWAS), namely restricted two-stage multi-locus multi-allele (RTM)-GWAS and mixed linear model (MLM)-GWAS, were used to dissect the genetic architecture of the agronomic traits based on 13,723 SNPs. Eleven quantitative trait loci (QTLs) for seven traits were identified using two models (RTM- and MLM-GWAS). Among them, five were considered stable QTLs that were identified in at least two environments using MLM-GWAS. One putative candidate gene (SETIT_006045mg, Chr4: 744,701-746,852) that can enhance grain weight per panicle was identified based on homologous gene comparison and gene expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished). In addition, homologous gene comparison and haplotype analysis identified one putative foxtail millet ortholog (SETIT_032906mg, Chr2: 5,020,600-5,029,771) with rice affecting the target traits. Two markers (cGWP6045 and kTGW2906) were developed and validated and can be used for marker-assisted selection of foxtail millet with high grain weight. The results provide a fundamental resource for foxtail millet genetic research and breeding and demonstrate the power of integrating RTM- and MLM-GWAS approaches as a complementary strategy for investigating complex traits in foxtail millet.

Depletion of L-Methionine in Foods with an Engineered Thermophilic Methionine γ-lyase Efficiently Inhibits Tumor Growth.

Dietary restriction of l-methionine, an essential amino acid, exerts potent antitumor effects on l-methionine-dependent cancers. However, dietary restriction of l-methionine has not been practical for human therapy because of the problem with the administration of l-methionine concentration in foods. Here, a thermophilic methionine γ-lyase (MGL), that catalyzes the cleavage of the C-S bond in l-methionine to produce α-ketobutyric acid, methanethiol, and ammonia was engineered from human cystathionine γ-lyase and almost completely depleted l-methionine at 65 °C, a temperature that accelerates the volatilization of methanethiol and its oxidation products. The high efficiency of l-methionine lysis may be attributed to the cooperative fluctuation and moderate the structural rigidity of 4 monomers in the thermophilic MGL, which facilitates l-methionine access to the entrance of the active site. Experimental diets treated with thermophilic MGL markedly inhibited prostate tumor growth in mice, and in parallel, the in vivo concentrations of l-methionine, its transformation product l-cysteine, and the oxidative stress indicator malondialdehyde significantly decreased. These findings provide a technology for the depletion of l-methionine in foods with an engineered thermophilic MGL, which efficiently inhibits tumor growth in mice.

Disaster experience and resident risk preference: Evidence from China household finance survey.

China is one of the countries hardest hit by disasters. Disaster shocks not only cause a large number of casualties and property damage but also have an impact on the risk preference of those who experience it. Current research has not reached a consensus conclusion on the impact of risk preferences. This paper empirically analyzes the effects of natural and man-made disasters on residents' risk preference based on the data of the China Household Financial Survey (CHFS) in 2019. The results indicate that: (1) Both natural and man-made disasters can significantly lead to an increase in the risk aversion of residents, and man-made disasters have a greater impact. (2) Education background plays a negative moderating role in the impact of man-made disasters on residents' risk preference. (3) Natural disaster experiences have a greater impact on the risk preference of rural residents, while man-made disaster experiences have a greater impact on the risk preference of urban residents. Natural disaster experiences make rural residents more risk-averse, while man-made disaster experiences make urban residents more risk-averse. The results provide new evidence and perspective on the negative impact of disaster shocks on the social life of residents.

Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Gerilimzumab (GB224), a recombinant humanized interleukin-6 monoclonal antibody, in healthy Chinese adults: A randomized controlled dose-escalation study.

OBJECTIVES: This study aimed to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of Gerilimzumab (GB224), a recombinant humanized IgG1λ monoclonal antibody against interleukin-6, in healthy Chinese adults. METHODS: Fifty-eight subjects were randomly assigned to receive a single subcutaneous dose of 2, 5, 10, 15, 20, 30 mg GB224 or placebo. Safety assessments were performed, and blood samples were collected for PK, PD, and immunogenicity analyses during a follow-up of 112 days. RESULTS: The most frequent adverse event was decreased fibrinogen (43.1%). GB224 was absorbed relatively fast with a median Tmax of 48 h (24-168 h) but eliminated slowly with a long mean half-life (839.38-981.63 h). Dose proportionality was shown to be in the dose range of 10-30 mg. A dose-dependent increase in serum interleukin-6 concentration from baseline was observed in the subjects receiving GB224. Only two subjects tested positive for antidrug antibodies after administration of GB224. CONCLUSION: GB224 had a well-tolerated safety profile, desirable PK, and a low immunogenicity following a single-dose subcutaneous administration in healthy Chinese subjects. These findings warrant further investigation.

Impacts of dissolved organic matter on the aggregation and photo-dissolution of cadmium pigment nanoparticles in aquatic systems.

Cadmium pigments are a group of inorganic pigments used in consumer products. The aggregation behavior and photo-dissolution process of cadmium pigment nanoparticles in aquatic systems control their environmental fate, which is largely unknown. Herein, we investigated the influence of dissolved organic matter (DOM) on the aggregation behavior and photo-dissolution process of CdS nanoparticles in aquatic systems. Bare CdS nanoparticles are prone to aggregation in both NaCl and CaCl2 solutions. DOM can remarkably increase the colloidal stability of CdS nanoparticles owing to the steric hindrance and enhanced electrostatic repulsion. With 10 mg/L Suwannee River natural organic matter (SRNOM), the colloidal stability of CdS nanoparticles is significantly enhanced in NaCl solutions (i.e., the critical coagulation concentration, CCCNa, is 707.2 mM). Suwannee River humic acid (SRHA) has a stronger stabilization effect than SRNOM due to its higher molecular weight and aromaticity. The Ca2+ cations can induce charge neutralization and structural compacting of DOM corona, efficiently reducing the colloidal stability of CdS nanoparticles. The CCCCa is 10.8 mM and 14.9 mM with 10 mg/L SRNOM and SRHA, respectively. Upon solar irradiation, the presence of a low concentration of SRNOM (3 mg/L) can enhance the photo-dissolution of CdS nanoparticles and the consequent Cd2+ leaching. This is caused by the facilitated electron transfer from CdS nanoparticles to O2 induced by SRNOM corona, leading to better electron-hole separation. However, a high concentration of SRNOM inhibited the photo-dissolution of CdS nanoparticles due to the strong inner filter effect and the scavenging of phototransients. The colloidal stability of SRNOM-coated CdS nanoparticles increases in NaCl but decreases in CaCl2 solutions after irradiation owing to the oxidation of SRNOM corona. Our results highlight the decisive role of DOM in the environmental fate of cadmium pigments.

The nitric oxide synthase gene negatively regulates biofilm formation in Staphylococcus epidermidis.

Staphylococcus epidermidis (S. epidermidis) is a clinically important conditioned pathogen that can cause a troublesome chronic implant-related infection once a biofilm is formed. The nitric oxide synthase (NOS) gene, which is responsible for endogenous nitric oxide synthesis, has already been found in the genome of S. epidermidis; however, the specific mechanisms associated with the effects of NOS on S. epidermidis pathogenicity are still unknown. The purpose of the current study was to investigate whether the NOS gene has an impact on biofilm formation in S. epidermidis. Bioinformatics analysis of the NOS gene was performed, and homologous recombination was subsequently employed to delete this gene. The effects of the NOS gene on biofilm formation of S. epidermidis and its underlying mechanisms were analyzed by bacterial growth assays, biofilm semiquantitative determination, Triton X-100-induced autolysis assays, and bacterial biofilm dispersal assays. Additionally, the transcription levels of fbe, aap, icaA, icaR and sigB, which are related to biofilm formation, were further investigated by qRT-PCR following NOS deletion. Phylogenetic analysis revealed that the NOS gene was conserved between bacterial species originating from different genera. The NOS deletion strain of S. epidermidis 1457 and its counterpart were successfully constructed. Disruption of the NOS gene resulted in significantly enhanced biofilm formation, slightly retarded bacterial growth, a markedly decreased autolysis rate, and drastically weakened bacterial biofilm dispersal. Our data showed that the fbe, aap and icaA genes were significantly upregulated, while the icaR and sigB genes were significantly downregulated, compared with the wild strain. Therefore, these data strongly suggested that the NOS gene can negatively regulate biofilm formation in S. epidermidis by affecting biofilm aggregation and dispersal.

Preparation and Performance Analysis of Transformer Aramid Nanopaper-Based Insulating Material Based on Deep Learning.

Transformers are an essential part of power production. Insulating paper began to be widely used in transformers in the 1990s. The superior aramid nanofiber as the matrix gives the aramid nano-insulating paper excellent mechanical properties, insulation performance, temperature resistance, and flexibility. At first, the heat resistance and service life of insulating paper should be satisfied for use in electrical equipment. With the continuous development of power equipment, people have put forward higher requirements on the properties of insulating paper, especially heat resistance and electrical properties. Insulation paper made of aramid fibers have better thermal stability and more advantages in electrical and mechanical properties, which can significantly improve the service life and safety of electrical appliances. The purpose of this article is to study the use of aramid nanopaper-based insulating materials in transformers to explore the effect of transformer discharge mechanism on aramid nanopaper-based insulating materials. This paper proposes to design multiple deep learning models to identify the discharge mode of the voltage transformer, find the characteristic signal, and carry out related tests on the discharge signal of different modes, and find the maximum temperature value of the aramid nanopaper-based insulating material for industrial use. The experimental results in this paper show that the aramid nanopaper-based insulating material can be used in transformers discharge detection well, and the safety rate is increased by 20%.

Associations between depressive symptoms and sleep duration for predicting cardiovascular disease onset: A prospective cohort study.

BACKGROUND: The joint effects of depressive symptoms and sleep on the risk of cardiovascular disease (CVD) are not well understood. The purpose of this study was to assess the combined impact of depressive symptoms and sleep duration on the incidence of CVD among middle-aged and older Chinese individuals. METHODS: Data were from the China Health and Longitudinal Study conducted in 2013, 2015, and 2018. A total of 9595 participants aged ≥ 45 years without a history of CVD in 2013 were included. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale (elevated depressive symptoms cutoff ≥ 10). Average sleep duration was self-reported. Logistic regression analyses adjusted for age, sex, marital status, education and other potential confounders were conducted. RESULTS: In total, 1072 (11.2%) participants reported CVD incidents over the 5-year period. Elevated depressive symptoms (OR = 1.49, 95% CI = 1.30-1.72) and short sleep duration (OR = 1.21, 95% CI = 1.05-1.40) were independently associated with an increased CVD risk in the fully adjusted model. Individuals with short sleep duration/low depressive symptoms (OR = 1.34, 95% CI = 1.12-1.60), short sleep duration/elevated depressive symptoms (OR = 1.70, 95% CI = 1.41-2.50), or long sleep duration/elevated depressive symptoms (OR = 2.13, 95% CI = 1.38-3.27) were more likely to develop CVD than those with normal sleep duration/low depressive symptoms. LIMITATIONS: Depressive symptoms and sleep duration were self-reported. CONCLUSIONS: A stronger risk of CVD was found when depressive symptoms and short or long sleep durations occurred together, suggesting that an integrated approach to sleep and depressive symptoms might be a feasible strategy for the prevention of CVD.

Pharmacokinetic bioequivalence, safety, and immunogenicity of GB222, a bevacizumab biosimilar candidate, and bevacizumab in Chinese healthy males: a randomized clinical trial.

BACKGROUND: This study was conducted to compare the similarity of the pharmacokinetics (PKs), safety, and immunogenicity of GB222, a potential bevacizumab biosimilar, to that of reference bevacizumab in Chinese healthy males. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, single-dose, parallel-group clinical trial performed in 84 Chinese healthy males, who were randomly assigned to receive a single infusion dose of 1 mg/kg GB222 or bevacizumab with an 84-days follow-up. The primary endpoint was the area under the plasma concentration-time curve (AUC) from zero to the last quantifiable concentration at time t (AUC0-t). The second endpoints were the safety and immunogenicity evaluation. The PK bioequivalence was verified by the 90% confidence intervals (CIs) of the geometrical mean (GM) ratio for AUC0-t falling within the bioequivalence margin, 80-125%. RESULTS: The PK profiles of GB222 and bevacizumab were comparable. The 90% CIs of GM ratio of GB222 to bevacizumab for AUC0-t was within the pre-specified bioequivalence margin. The most common treatment-related adverse event was sinus bradycardia. Seventeen subjects (20.2%) tested positive for anti-drug antibodies (ADAs). CONCLUSION: GB222 was found to be comparable to bevacizumab in terms of PKs, safety, and immunogenicity for Chinese healthy males. TRIAL REGISTRATION: ChiCTR-IIR-17,011,143.

High-Throughput Method for Natural Organic Matter Hydrophobicity Assessment Using an Ionic Liquid-Based Aqueous Two-Phase System.

Hydrophobicity of natural organic matter (NOM) is one of its fundamental properties that influence the environmental fate of pollutants and the performance of many water treatment unit processes. In this study, a high-throughput method was developed for NOM hydrophobicity measurement based on the phase separation technique in the 96-well format. It measures the partition coefficients of NOM (KATPS,IL) in an ionic liquid (IL)-based aqueous two-phase system (ATPS). The ATPS was made of 1-butyl-3-methylimidazole bromide solution and a salt solution containing potassium phosphate monobasic and potassium phosphate dibasic. The partition of NOM in IL-based ATPS is mainly affected by its hydrophobicity. log KATPS,IL linearly correlated with the commonly used NOM hydrophobicity scales, including (O + N)/C, O/C, and aromatic carbons. KATPS,IL provided a more accurate assessment of NOM hydrophobicity than spectroscopic indices. Furthermore, KATPS,IL can predict the organic carbon-water partition coefficients for hydrophobic organic chemical sorption to NOM based on the two-phase system model. The high-throughput KATPS,IL measurement and the two-phase system model can be applied to real surface water samples. Our results suggest that the proposed high-throughput method has great potential to be applied to monitor NOM hydrophobicity for environmental risk assessment and water treatment purposes.

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3.

BACKGROUND: Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. METHODS: In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. RESULTS: IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. CONCLUSIONS: These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.

Comparative efficacy and safety of 8 GLP-1RAs in patients with type 2 diabetes: A network meta-analysis.

AIMS: To inform clinical practice by comparing and ranking the lowing blood glucose and weight-loss abilities of 8 glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, and CENTRAL from database inception to April 13, 2021. The outcomes were Δ HbA1c, Δ weight, adverse events [AE] withdrawals, and incidence of hypoglycemia. We estimated standardized mean differences [SMD] and summary odds ratios (ORs) using frequentist network meta-analysis with random effects. RESULTS: Retrieved trials included 11,126 patients, the overall mean age was 56.7 ± 10.36 years old. In terms of efficacy, all GLP-1RAs were more effective than the placebo except albiglutide-30 mg QW (Δ weight: SMD -0.26 kg [95 %CI: -1.10, 0.59 kg). When it came to safety, oral semaglutide-14mgQD, semaglutide-1mgQW, Liraglutide-1.8mgQD, and Exenatide-2ugBID were associated with an increased risk of AE withdrawals. And GLP-1RAs were associated with a higher incidence of hypoglycemia than placebo except albiglutide-30mgQW and orally administered semaglutide-14mgQD. CONCLUSION: Overall GLP-1RAs were more efficacious than placebo in patients with T2D on efficacy. Unfortunately, differences between GLP1-RAs regarding safety were mostly not significant. We may realize the individualized GLP-1RAs administration based on blood glucose level and obesity degree.

Research of Fluorescent Properties of a New Type of Phosphor with Mn2+-Doped Ca2SiO4.

Fluorescent optical fiber temperature sensors have attracted extensive attention due to their strong anti-electromagnetic interference ability, good high-voltage insulation performance, and fast response speed. The fluorescent material of the sensor probe directly determines the temperature measurement effect. In this paper, a new type of fluorescent material with a Mn2+-doped Ca2SiO4 phosphor (CSO:Mn2+) is synthesized via the solid-state reaction method at 1450 °C. The X-ray diffraction spectrum shows that the sintered sample has a pure phase structure, although the diffraction peaks show a slight shift when dopants are added. The temperature dependence of the fluorescence intensity and lifetime in the range from 290 to 450 K is explored with the help of a fluorescence spectrometer. Green emission bands peaking at 475 and 550 nm from Mn2+ are observed in the fluorescence spectra, and the intensity of emitted light decreases as the temperature rises. The average lifetime of CSO:Mn2+ is 17 ms, which is much higher than the commonly used fluorescent materials on the market. The fluorescence lifetime decreases with increasing temperature and shows a good linear relationship within a certain temperature range. The research results are of great significance to the development of a new generation of fluorescence sensors.

Spatial and seasonal patterns of dissolved organic matter hydrophobicity in Lake Taihu revealed by the aqueous two-phase system.

The hydrophobicity of dissolved organic matter (DOM) is a key property influencing the environmental risks of organic pollutants. Our understanding of the spatial and seasonal pattern of DOM hydrophobicity in aquatic systems and the major controlling factors is still limited. In this study, the hydrophobicity of 124 DOM samples collected from northern Lake Taihu, a typical eutrophic lake, was quantified using the partition coefficient of DOM in the aqueous two-phase system (KATPS). The results revealed high-resolution spatial patterns and seasonal variations of DOM hydrophobicity in Lake Taihu. The riverine input, algae activity, and photodegradation were identified as important processes shaping the spatial and seasonal pattern of DOM hydrophobicity. The riverine input and algae activity strongly affected DOM hydrophobicity in the west part and the central area of the lake. Photodegradation process played a significant role in DOM hydrophobicity in the east part of the lake in summer. The high-resolution spatial and seasonal pattern of the hydrophobic organic pollutant partition affinity of DOM (KOC) was assessed based on the two-phase system model and the KATPS dataset. The KOC values vary significantly in Lake Taihu between spring and summer, especially in the Zhushan Bay and east coast areas, highlighting the need for considering DOM dynamics in sorption assessment. Our results detailly profiled the spatial and seasonal patterns of DOM hydrophobicity and sorption behavior and elucidated the major controlling factors, which is crucial for environmental risk assessment.

A Systematic Review and Meta-Analysis: Safety and Efficacy of Mesenchymal Stem Cells Therapy for Heart Failure.

BACKGROUND: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating Heart Failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy are not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. METHODS: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized Controlled Trials (RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model by the use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was safely assessed by death and rehospitalization and the secondary outcome was efficacy, which was assessed by six-minute walk distance and Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-systolic Volume (LVESV), Left Ventricular End-diastolic Volume (LVEDV) and Brain Natriuretic Peptide (BNP). RESULTS: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT. MSCs transplantation significantly improved Left Ventricular Ejection Fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased Left Ventricular End-Systolic Volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, - 12.83], p<0.00001) and Left Ventricular End-Diastolic Volume (LVEDV) by 5.78 ml (MD [95% CI]=- 5.78[-12.00, 0.43], p=0.07), in the MSCs group, BNP was decreased by 133.51 pg/ml MD [95% CI]= - 133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. CONCLUSION: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure are safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.

rHuPH20-facilitated subcutaneous administration of monoclonal antibodies in cancer therapy.

Aim: This meta-analysis aimed to evaluate the pharmacokinetics, efficacy, safety and immunogenicity of rHuPH20-facilitated subcutaneous (SC) administration of monoclonal antibody compared with intravenous (IV) administration for patients with cancer. Materials & methods: Outcomes included trough concentrations (Ctrough), overall response rate, adverse events, serious adverse events and antidrug antibody positivity rate. Subgroup analysis was also performed. Results: Five studies involving 1575 participants (788/787) were included. All studies met the non-inferiority criterion in Ctrough. No significant differences were observed in overall response rate (p = 0.12), adverse events (p = 0.05), and severe adverse events (p = 0.73) between SC and IV groups. The SC group also had lower immunogenicity than the IV group. Conclusion: rHuPH20-facilitated subcutaneous administration of monoclonal antibody is highly similar to IV administration in terms of pharmacokinetics, efficacy, and safety, but with lower immunogenicity.

Randomised, double-blind, multicentre, phase â /â ¡ dose escalation and expansion trial of GR1501 in patients with plaque psoriasis: study protocol.

INTRODUCTION: Psoriasis is a life-long, immune-mediated disease that greatly reduces the quality of life of patients. Plaque psoriasis is the most common form of psoriasis. Treatment options for plaque psoriasis with good tolerance and sufficient response remain profoundly limited. Based on mechanistic findings that suggest the key pathogenic role of interleukin (IL)-17 in plaque psoriasis, we hypothesise that GR1501, a new monoclonal antibody (IL-17A targeted), will be an efficacious treatment for plaque psoriasis. This phase I/II trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and preliminary efficacy of GR1501. METHODS AND ANALYSIS: A multicentre, randomised, double-blind, phase I/II dose escalation and expansion trial will be conducted at four hospitals in China. In total, 226 patients with plaque psoriasis will be enrolled in the study, with 46 cases in the dose-escalation stage and 180 cases randomised to GR1501 or the placebo in a 3:1 ratio in the expansion cohort. The primary outcomes are safety and tolerability; the secondary outcomes include pharmacokinetics, immunogenicity and efficacy. ETHICS AND DISSEMINATION: The study is in accordance with the Declaration of Helsinki, and the ethics approvals of the protocol have been obtained from the ethics committees of all participating centres, including Peking University People's Hospital, Chinese PLA General Hospital, The First Affiliated Hospital, College of Medicine, Zhejiang University and the Second Xiangya Hospital of Central South University. The findings of the study will be presented in published journals or at scientific conferences or meetings. TRIAL REGISTRATION NUMBER: ChiCTR1800017956.