Can China's carbon generalized system of preferences reduce urban residents' carbon emissions? Evidence from a quasi-natural experiment.

The carbon generalized system of preferences (CGSP) is an innovative incentive mechanism implemented by the Chinese government, which has also become an important part of carbon emission reduction at the living end, and it is of great significance to study whether the Pilot Policy can reduce the carbon emissions of residents. This study firstly accounts for the total carbon emissions and per capita carbon emissions of the residents of 284 cities in China, and on this basis, adopts the SCM method to quantitatively study and analyze the overall and local implementation effects of CGSP in China by taking the first batch of CGSP pilots in China as an example, and further applies the mediation effect model to test the pathways of the role of CGSP. The main findings of the study are as follows: (1) During the period of 2010-2020, the total carbon emissions from urban residents' living in China showed a yearly growth trend, from 36,623.98 ×10-2Mt in 2010-85,241.20 ×10-2Mt in 2020, an increase of 8.83%. Total carbon emissions present a structural difference of "electricity consumption > central heating > private transport > gas (oil, natural gas) consumption". (2) Overall, the implementation of the CGSP had a robust positive impact on the overall carbon emission reduction in the pilot cities, with an average annual emission reduction effect value of 36.53 ×10-2Mt. Locally, the annual net policy effect values of Dongguan, Zhongshan, Heyuan, and Guangzhou are 6169.79 ×10-2, 26,600.17 ×10-2, 17,081.34 ×10-2 and 9393.36 ×10-2Mt respectively. (3) CGSP has a good carbon emission reduction effect by suppressing the impact on residents' carbon emissions through enhancing the city's innovation capacity and promoting electricity saving and consumption reduction, while the mediating effect played by the promotion of green and low-carbon travel in the pilot policy is not significant. Finally, based on the research findings, relevant suggestions are targeted.

Solar-assisted selective separation and recovery of precious group metals from deactivated air purification catalysts.

The mitigation of environmental and energy crises could be advanced by reclaiming platinum group precious metals (PGMs) from decommissioned air purification catalysts. However, the complexity of catalyst composition and the high chemical inertness of PGMs significantly impede this process. Consequently, recovering PGMs from used industrial catalysts is crucial and challenging. This study delves into an environmentally friendly approach to selectively recover PGMs from commercial air purifiers using photocatalytic redox technology. Our investigation focuses on devising a comprehensive strategy for treating three-way catalysts employed in automotive exhaust treatment. By meticulously pretreating and modifying reaction conditions, we achieved noteworthy results, completely dissolving and separating rhodium (Rh), palladium (Pd), and platinum (Pt) within a 12-h time frame. Importantly, the solubility selectivity persists despite the remarkably similar physicochemical properties of Rh, Pd, and Pt. To bolster the environmental sustainability of our method, we harness sunlight as the energy source to activate the photocatalysts, facilitating the complete dissolution of precious metals under natural light irradiation. This eco-friendly recovery approach demonstrated on commercial air purifiers, exhibits promise for broader application to a diverse range of deactivated air purification catalysts, potentially enabling implementation on a large scale.

Interlayer Structure Manipulation of FeOCl/MXene with Soft/Hard Interface Design for Safe Water Production Using Dechlorination Battery Deionization.

Suffering from the susceptibility to decomposition, the potential electrochemical application of FeOCl has greatly been hindered. The rational design of the soft-hard material interface can effectively address the challenge of stress concentration and thus decomposition that may occur in the electrodes during charging and discharging. Herein, interlayer structure manipulation of FeOCl/MXene using soft-hard interface design method were conducted for electrochemical dechlorination. FeOCl was encapsulated in Ti3C2Tx MXene nanosheets by electrostatic self-assembly layer by layer to form a soft-hard mechanical hierarchical structure, in which Ti3C2Tx was used as flexible buffer layers to relieve the huge volume change of FeOCl during Cl- intercalation/deintercalation and constructed a conductive network for fast charge transfer. The CDI dechlorination system of FeOCl/Ti3C2Tx delivered outstanding Cl- adsorption capacity (158.47 ± 6.98 mg g-1), rate (6.07 ± 0.35 mg g-1 min-1), and stability (over 94.49% in 30 cycles), and achieved considerable energy recovery (21.14 ± 0.25%). The superior dechlorination performance was proved to originate from the Fe2+/Fe3+ topochemical transformation and the deformation constraint effect of Ti3C2Tx on FeOCl. Our interfacial design strategy enables a hard-to-soft integration capacity, which can serve as a universal technology for solving the translational problem of electrode volume expansion.

Natural tea polyphenol functionalized graphene anode for simultaneous power production and degradation of methyl orange dye in microbial fuel cells.

The microbial fuel cell (MFCs) has dual functions, capable of achieving dye decolorization and synchronous power generation. Despite these advantages, the MFCs have faced challenges related to low electron transfer efficiencies and limited dye treatment capacity in wastewater applications. This work introduces an innovative approach by employing reduced graphene oxide-modified carbon cloth (TP-RGO@CC) anodes, utilizing tea polyphenols as the reducing agent. This modification significantly enhances the hydrophilicity and biocompatibility of the anodes. The MFC equipped with the TP-RGO@CC anode demonstrated a remarkable increase in the maximum power density, reaching 773.9 mW m-2, representing a 22% improvement over the plain carbon cloth electrode. The decolorization rate of methyl orange (50 mg L-1, pH 7) reached 99% within 48 h. Biodiversity analysis revealed that the TP-RGO@CC anode selectively enriched electrogens producing and organic matter-degrading bacteria, promoting a dual mechanism of dye decolorization, degradation, and simultaneous electro-production at the anode. This work highlights advanced anode materials that excel in effective pollutant removal, energy conversion, and biomass reuse.

The association between urinary incontinence and suicidal ideation: Findings from the National Health and Nutrition Examination Survey.

BACKGROUND: Urinary incontinence (UI) might be linked to suicidal ideation, but we do not yet have all the relevant details. This study aimed to dig deeper into the connection between UI and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We examined 31,891 participants aged ≥ 20 years from NHANES 2005-2018 who provided complete information. We used standardized surveys to check for UI and signs of suicidal ideation. To better understand this relationship, we used statistical tools such as multivariable logistic regression, subgroup analysis, and sensitivity analyses. RESULTS: Among the 31,891 participants, 28.9% reported UI and 10.7% reported suicidal ideation. Those with UI exhibited a significantly greater incidence of suicidal ideation (15.5%) than did those without UI (8.8%, P < 0.001). After adjusting for various factors, including age, sex, marital status, socioeconomic status, educational level, lifestyle factors, and chronic comorbidities, UI remained significantly associated with suicidal ideation (OR:1.54, 95% CI = 1.39-1.7, P < 0.001). Among all types of UI, MUI participants were more likely to experience suicidal ideation. Compared with no UI, higher odds of suicidal ideation suffered from MUI (OR:2.11, 95%CI:1.83-2.44, P < 0.001), SUI (OR:1.4, 95%CI:1.19-1.65, P < 0.001), UUI(OR:1.37,95%CI:1.16-1.62, P < 0.001) after full adjustment. With the exception of individuals living with a partner, the remaining subgroups exhibited a positive correlation between urinary incontinence and suicidal ideation, considering that factors such as age, sex, and prevalent comorbidities such as hypertension, depression, and diabetes did not reveal any statistically significant interactions (all P > 0.05). Sensitivity analyses, incorporating imputed missing covariates, did not substantially alter the results (OR: 1.53, 95% CI: 1.4-1.68, P < 0.001). CONCLUSION: Urinary incontinence may correlate with increased suicidal ideation risk, priority screening for suicidal ideation and timely intervention are essential for individuals with urinary incontinence, but prospective studies are needed to verify the results.

Nanoporous Carbon Materials Derived from Zanthoxylum Bungeanum Peel and Seed for Electrochemical Supercapacitors.

In order to prepare biomass-derived carbon materials with high specific capacitance at a low activation temperature (≤700 °C), nanoporous carbon materials were prepared from zanthoxylum bungeanum peels and seeds via the pyrolysis and KOH-activation processes. The results show that the optimal activation temperatures are 700 °C and 600 °C for peels and seeds. Benefiting from the hierarchical pore structure (micropores, mesopores, and macropores), the abundant heteroatoms (N, S, and O) containing functional groups, and plentiful electrochemical active sites, the PAC-700 and SAC-600 derive the large capacities of ~211.0 and ~219.7 F g-1 at 1.0 A g-1 in 6 M KOH within the three-electrode configuration. Furthermore, the symmetrical supercapacitors display a high energy density of 22.9 and 22.4 Wh kg-1 at 7500 W kg-1 assembled with PAC-700 and SAC-600, along with exceptional capacitance retention of 99.1% and 93.4% over 10,000 cycles at 1.0 A g-1. More significantly, the contribution here will stimulate the extensive development of low-temperature activation processes and nanoporous carbon materials for electrochemical energy storage and beyond.

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Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase ï¼»MMPï¼½-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-ß1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca2+/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.

Oncofetal SNRPE promotes HCC tumorigenesis by regulating the FGFR4 expression through alternative splicing.

BACKGROUND: Due to insufficient knowledge about key molecular events, Hepatocellular carcinoma (HCC) lacks effective treatment targets. Spliceosome-related genes were significantly altered in HCC. Oncofetal proteins are ideal tumor therapeutic targets. Screening of differentially expressed Spliceosome-related oncofetal protein in embryonic liver development and HCC helps discover effective therapeutic targets for HCC. METHODS: Differentially expressed spliceosome genes were analysis in fetal liver and HCC through bioinformatics analysis. Small nuclear ribonucleoprotein polypeptide E (SNRPE) expression was detected in fetal liver, adult liver and HCC tissues. The role of SNRPE in HCC was performed multiple assays in vitro and in vivo. SNRPE-regulated alternative splicing was recognized by RNA-Seq and confirmed by multiple assays. RESULTS: We herein identified SNRPE as a crucial oncofetal splicing factor, significantly associated with the adverse prognosis of HCC. SOX2 was identified as the activator for SNRPE reactivation. Efficient knockdown of SNRPE resulted in the complete cessation of HCC tumorigenesis and progression. Mechanistically, SNRPE knockdown reduced FGFR4 mRNA expression by triggering nonsense-mediated RNA decay. A partial inhibition of SNRPE-induced malignant progression of HCC cells was observed upon FGFR4 knockdown. CONCLUSIONS: Our findings highlight SNRPE as a novel oncofetal splicing factor and shed light on the intricate relationship between oncofetal splicing factors, splicing events, and carcinogenesis. Consequently, SNRPE emerges as a potential therapeutic target for HCC treatment. Model of oncofetal SNRPE promotes HCC tumorigenesis by regulating the AS of FGFR4 pre-mRNA.

Effect of genotyping errors on linkage map construction based on repeated chip analysis of two recombinant inbred line populations in wheat (Triticum aestivum L.).

Linkage maps are essential for genetic mapping of phenotypic traits, gene map-based cloning, and marker-assisted selection in breeding applications. Construction of a high-quality saturated map requires high-quality genotypic data on a large number of molecular markers. Errors in genotyping cannot be completely avoided, no matter what platform is used. When genotyping error reaches a threshold level, it will seriously affect the accuracy of the constructed map and the reliability of consequent genetic studies. In this study, repeated genotyping of two recombinant inbred line (RIL) populations derived from crosses Yangxiaomai × Zhongyou 9507 and Jingshuang 16 × Bainong 64 was used to investigate the effect of genotyping errors on linkage map construction. Inconsistent data points between the two replications were regarded as genotyping errors, which were classified into three types. Genotyping errors were treated as missing values, and therefore the non-erroneous data set was generated. Firstly, linkage maps were constructed using the two replicates as well as the non-erroneous data set. Secondly, error correction methods implemented in software packages QTL IciMapping (EC) and Genotype-Corrector (GC) were applied to the two replicates. Linkage maps were therefore constructed based on the corrected genotypes and then compared with those from the non-erroneous data set. Simulation study was performed by considering different levels of genotyping errors to investigate the impact of errors and the accuracy of error correction methods. Results indicated that map length and marker order differed among the two replicates and the non-erroneous data sets in both RIL populations. For both actual and simulated populations, map length was expanded as the increase in error rate, and the correlation coefficient between linkage and physical maps became lower. Map quality can be improved by repeated genotyping and error correction algorithm. When it is impossible to genotype the whole mapping population repeatedly, 30% would be recommended in repeated genotyping. The EC method had a much lower false positive rate than did the GC method under different error rates. This study systematically expounded the impact of genotyping errors on linkage analysis, providing potential guidelines for improving the accuracy of linkage maps in the presence of genotyping errors.

[Analysis on Hydrochemical Evolution of Shallow Groundwater East of Yongding River in Fengtai District, Beijing].

In order to enhance the support for groundwater development and utilization, as well as pollution control and prevention in Fengtai District, Beijing, a comprehensive study was conducted based on long-term monitoring data of shallow groundwater in the eastern area of Yongding River during the dry season. The mathematical statistics, Piper diagram, Gibbs diagram, and ion ratio analysis and other methods were employed to explore the pattern of groundwater hydrochemical evolution, the formation mechanism, and sources of pollution in Fengtai District. The findings were as follows:① Overall, the current groundwater quality in the study area was poor. The average concentration of each index in groundwater increased and then decreased from 1976 to the present. The pollution range of Cl-, SO42-, and TH generally expanded, whereas the pollution range of TDS and NO3- expanded before 2005 and then decreased with 2005 as the turning point. ② The hydrochemical types of groundwater samples displayed a complex regional variation each year, as well as along the groundwater direction. The dominant anion in groundwater was HCO3-, and the dominant cation was Ca2+ each year. The number of groundwater hydrochemical types in 1976 was 8, in which the predominant type was HCO3·SO4-Ca·Mg·Na, accounting for 40%. However, the number of groundwater hydrochemical types in 2021 was 17, in which the predominant type was HCO3·Cl·SO4-Ca·Na·Mg, accounting for 23.88%. The groundwater hydrochemical type showed a complex trend within the region and upstream along the flow direction each year, whereas the migration characteristics of groundwater samples, as depicted on the Piper diagram, indicated that the hydrochemical components of groundwater were significantly affected by human activities during its evolution. ③ The groundwater chemistry in the study area was influenced by both rock weathering and evaporative crystallization processes, with evaporation playing a major role. The alternation of groundwater cations was relatively weak, and the dissolution of carbonate minerals served as the primary source of Ca2+ and Mg2+. ④ The ion ratio analysis suggested that exogenous sources, mainly agricultural activities and urban sewage, contributed to the input of NO3- and Cl-. The pollution impact from agricultural activities was significant before 2005, which aligned with the historical presence of numerous seepage pits, seepage wells, and direct discharge of industrial and domestic sewage for irrigation purposes in the study area. These activities were closely associated with the high levels of pollution. However, pollution input from agricultural activities notably decreased in 2021, likely due to the effective implementation of water environmental protection programs and action plans in recent years.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

Single-dose Administration of Recombinant Human Thrombopoietin Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated with 3 Gy Gamma Radiation.

We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 µg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 µg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 µg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 µg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage.

Responses and resistance capacity of Solanum nigrum L. mediated by three ecological category earthworms in metal-[Cd-As-Cu-Pb]-contaminated soils of North China.

Earthworms play vital functions affecting plant growth and metal accumulation from downground to aboveground. Soil metal mobilization may be combined with use of earthworm and hyperaccumulator-Solanum nigrum to improve its remediation efficiency. Understanding the effects of specific-species earthworm belonging to different ecological categories on mechanisms underlying of S. nigrum is critical for metal-polluted remediation. However, seldom studies concerned earthworm-assisted phytoremediation of metal contaminated soil in Northern China. This study investigated the effects of earthworm (Eisenia fetida, Amynthas hupeiensis and Drawida gisti) on S. nigrum with exposure to uncontaminated and [Cd-As-Cu-Pb]-contaminated soil (referred to as S0 and S1) for 60 days, respectively. In S1 soil, A. hupeiensis (anecic) had stronger effects on growth and metal accumulation in the organs (root, stem, and leaf) of S. nigrum than D. gisti (endogeic) and E. fetida (epigeic), attributing to their ecological category. The BAF values of S. nigrum were generally ranking in Cd (0.66-5.13) > As (0.03-1.85) > Cu (0.03-0.06) > Pb (0.01-0.05); the BAFCd values were ranking in leaf (2.34-5.13) > root (1.96-4.14) > stem (0.66-1.33); BAFAs, BAFCu, and BAFPb were root (0.04-1.63) > stem (0.01-0.09) ≈ leaf (0.01-0.06). A. hupeiensis decreased the TF values of S. nigrum from the roots to the shoots. Co-effects of metal stress and earthworm activity on metal uptake by shoots suggested that A. hupeiensis increased the uptake of As, Cu, and Pb (by 56.3 %, 51.5 %, and 16.2 %, p < 0.05), but not Cd, which appeared to remain steady for prolonged durations. Alterations in the integrated biomarker response index version 2 (IBRv2) values demonstrated that A. hupeiensis (12.65) improved the resistance capacity (stimulated GSH, SnGS1, and SnCu-SOD) of S. nigrum under metal-containing conditions, compared with E. fetida and D. gisti (IBRv2 were 9.61 and 9.11). This study may provide insights into the patterns of 'soil-earthworm-plant system' on improving remediation efficiency of S. nigrum, from the perspective of earthworm ecological niche partitioning.

Utilization of composite particles with customizable cross-linked lignin patches for dental cleansing.

Lignin, a natural polyphenol polymer, is a biocompatible, cost-effective and accessible material. To fully utilize the benefits of lignin, it is crucial to transform its complex macromolecules into nanoscale particles in a single solvent. In this research, an assembly-mediated internal cross-linking method in single solvent was proposed to manufacture cross-linked lignin colloidal particles with nanoscale particle size controlled to be around 50 nm. Then, cross-linked lignin composite particles with a unique "patchy" structure for dental cleansing were obtained by rapidly grafting the cross-linked lignin colloidal particles onto the surface of silica microspheres through the bridging effect of silane coupling agent. The resulting composite particles have rivets with adjustable hardness, significantly lower than traditional abrasives like silica in both hardness and modulus. Through the group cleansing behavior of soft interlocking, a breakthrough has been achieved in the high solid content agglomeration friction mode of traditional abrasives, which effectively reduces tooth wear and exhibits an excellent plaque removal effect.

Phosphorus Modulated Peroxidase-Like Activity of Carbon Dots for Colorimetric Detection of Acid Phosphatase.

The precise regulation of nanoenzyme activity is of great significance for application to biosensing analysis. Herein, the peroxidase-like activity of carbon dots was effectively modulated by doping phosphorus, which was successfully employed for sensitive, selective detection of acid phosphatase (ACP). Phosphorus-doped carbon dots (P-CDs) with excellent peroxidase-like activity were synthesized by a one-pot hydrothermal method, and the catalytic activity could be easily modulated by controlling the additional amount of precursor phytic acid. P-CDs could effectively catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxidation products in the presence of hydrogen peroxide. While ACP was able to catalyze the hydrolysis of L-ascorbyl-2-phosphate trisodium salt (AAP) to produce ascorbic acid (AA), which inhibited the peroxidase-like activity of P-CDs, by combining P-CDs nanoenzymes and ACP-catalyzed hydrolysis the colorimetric method was established for ACP detection. The absorbance variation showed a good linear relationship with ACP concentration in the range of 0.4-4.0 mU/mL with a limit of detection at 0.12 mU/mL. In addition, the method was successfully applied to detect ACP in human serum samples with recoveries in the range of 98.7-101.6%. The work provides an effective strategy for regulating nanoenzymes activity and a low-cost detection technique for ACP.

Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3.

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

S-9-PAHSA's neuroprotective effect mediated by CAIII suppresses apoptosis and oxidative stress in a mouse model of type 2 diabetes.

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

Incorporating participants' welfare into sequential multiple assignment randomized trials.

Dynamic treatment regimes (DTRs) are sequences of decision rules that recommend treatments based on patients' time-varying clinical conditions. The sequential, multiple assignment, randomized trial (SMART) is an experimental design that can provide high-quality evidence for constructing optimal DTRs. In a conventional SMART, participants are randomized to available treatments at multiple stages with balanced randomization probabilities. Despite its relative simplicity of implementation and desirable performance in comparing embedded DTRs, the conventional SMART faces inevitable ethical issues, including assigning many participants to the empirically inferior treatment or the treatment they dislike, which might slow down the recruitment procedure and lead to higher attrition rates, ultimately leading to poor internal and external validities of the trial results. In this context, we propose a SMART under the Experiment-as-Market framework (SMART-EXAM), a novel SMART design that holds the potential to improve participants' welfare by incorporating their preferences and predicted treatment effects into the randomization procedure. We describe the steps of conducting a SMART-EXAM and evaluate its performance compared to the conventional SMART. The results indicate that the SMART-EXAM can improve the welfare of the participants enrolled in the trial, while also achieving a desirable ability to construct an optimal DTR when the experimental parameters are suitably specified. We finally illustrate the practical potential of the SMART-EXAM design using data from a SMART for children with attention-deficit/hyperactivity disorder.

Overexpression of miR-506-3p reversed doxorubicin resistance in drug-resistant osteosarcoma cells.

Background and objective: Osteosarcoma is a common primary malignant tumor of bone, and doxorubicin is one of the most widely used therapeutic drugs. While the problem of doxorubicin resistance limits the long-term treatment benefits in osteosarcoma patients. The role of miRNAs and their target genes in osteosarcoma have become increasingly prominent. Currently, there is no report on miR-506-3p reversing doxorubicin resistance by targeting STAT3 in osteosarcoma. The purpose of this study was to investigate the molecular mechanism that overexpression of miR-506-3p reverses doxorubicin resistance in drug-resistant osteosarcoma cells. Methods: Doxorubicin-resistant osteosarcoma cells (U-2OS/Dox) were constructed by intermittent stepwise increasing stoichiometry. The target genes of miR-506-3p were predicted by bioinformatics approach and the targeting relationship between miR-506-3p and STAT3 was detected using dual luciferase reporter assay. U-2OS/Dox cells were treated with miR-506-3p overexpression and STAT3 silencing respectively. Then Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of JAK2/STAT3 signaling pathway, drug-resistant and apoptotic associated molecules. The migration and invasion were assessed by cell scratch assay and transwell assay. The cell proliferative viability and apoptosis were investigated by CCK8 assay and flow cytometry assay. Results: U-2OS/Dox cells were successfully constructed with a 14.4-fold resistance. MiR-506-3p is directly bound to the 3'-UTR of STAT3 mRNA. Compared with U-2OS cells, the mRNA expression of miR-506-3p was reduced in U-2OS/Dox cells. Overexpression of miR-506-3p decreased the mRNA expression levels of JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and decreased the protein expression levels of p-JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin and Bcl-2, and conversely increased Bax expression. It also inhibited the proliferation, migration and invasion of U-2OS/Dox cells and promoted cells apoptosis. The results of STAT3 silencing experiments in the above indicators were consistent with that of miR-506-3p overexpression. Conclusion: Overexpression of miR-506-3p could inhibit the JAK2/STAT3 pathway and the malignant biological behaviors, then further reverse doxorubicin resistance in drug-resistant osteosarcoma cells. The study reported a new molecular mechanism for reversing the resistance of osteosarcoma to doxorubicin chemotherapy and provided theoretical support for solving the clinical problems of doxorubicin resistance in osteosarcoma.

Exposure to particulate matter may affect semen quality via trace metals: Evidence from a retrospective cohort study on fertile males.

Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2.5 and PM10 exposure levels were positively associated with arsenic (As), mercury (Hg), lanthanum (La), praseodymium (Pr), neodymium (Nd) but negatively associated with vanadium (V), magnesium (Mg), strontium (Sr), barium (Ba) in semen. It was also found that most of the elements were associated with total sperm number, followed by sperm concentration. Redundancy analysis (RDA) also determined several strong positive correlations or negative correlations between 1-year PM exposure and trace metals. Mediation analysis found that trace metals had a potentially compensatory or synergetic indirect effect on the total effect of the association between 1-year PM exposure and semen quality. The retrospective cohort study provides long-term PM exposure that may cause abnormal semen quality by affecting seminal plasma element levels.