Effective peroxymonosulfate activation by lithium cobaltite recovered from spent lithium-ion batteries for enhanced carbamazepine degradation in a wide pH range.

Considering the high cost and complicated recycling process of spent lithium-ion batteries (SLIBs), transforming SLIBs into environment functional materials may be a wise approach. Herein, lithium cobaltite (LCO) cathode powders recovered from SLIBs were used to activate peroxymonosulfate (PMS) for removing carbamazepine (CBZ). The recovered LCO enables a 98.2% removal efficiency of CBZ (2.5 mg/L) within 10 min, which was effective at a broader pH range (pH = 5.0-11.0). The influence of key factors (initial pH, PMS, and catalyst dosage) and coexisting substances (SO42-, H2PO4-, NO3-, Cl-, HCO3-, and HA) on CBZ degradation were examined in detail. The primary radical species during the degradation of CBZ were proved to be 1O2, SO4-, and.OH that generated from PMS activation initiated by the valence change of Co in recovered LCO. The recovered LCO displayed excellent reusability with about 80.0% removal of CBZ after six cycles. Homogeneous activation of PMS mainly contributed to CBZ degradation in the first run, but the recovered LCO catalyst dominated the heterogeneous activation of PMS for the degradation of CBZ in the second to sixth run. Finally, the CBZ degradation pathways were presented based on the identified intermediates. This research has offered a new strategy of "treating wastes with wastes" to maximize the recycling of electronic wastes to remove emerging pollutants.

Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.

Cadmium Minimization in Grains of Maize and Wheat Grown on Smelting-Impacted Land Ameliorated by Limestone.

Cadmium (Cd) contamination in agricultural soils has emerged as a significant concern, particularly due to its potential impact on plant-based food. Soil pH reductions can exacerbate Cd mobility, leading to excessive accumulation in crops. While liming has been demonstrated as an effective method to mitigate Cd accumulation in rice grains in acid soils of southern China, its efficacy in remediating acid soils in northern China remains unclear. In this study, a multi-year field experiment was conducted on farmland impacted by zinc ore smelting at coordinates of 33.92° N 112.46° E to investigate the use of limestone for controlling Cd accumulation in wheat and maize grains. The results indicated that applying 7.5 t ha-1 of limestone significantly raised the soil pH from 4.5 to 6.8 as anticipated. Different rates of limestone application (2.25, 4.45, and 7.50 t ha-1) reduced Cd bioavailability in the soil by 20-54%, and Cd accumulation in wheat grains by 5-38% and maize grains by 21-63%, without yield penalty. The remediation effects were sustained for at least 27 months, highlighting limestone as a promising ameliorant for smelting-affected farmland in northern China.

The efficacy, safety, and beneficiary population of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer patients: A comparative cohort study.

AIM: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer (RPR-OC) patients. METHODS: This study retrieved 67 RPR-OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. RESULTS: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression-free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5-6.3) months in apatinib + chemo group and 3.8 (2.0-5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5-24.5) months in apatinib + chemo group and 13.6 (8.6-18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). CONCLUSION: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR-OC patients.

Comprehensive analysis of the gut microbiota in patients with chronic obstructive pulmonary disease of varying severity-A prospective, observational study.

Accumulating evidence has highlighted the influence of the gut microbiota on lung immunity. We examined the effects of changes in intestinal microecology on the development of Chronic Obstructive Pulmonary Disease (COPD) and identified microbial biomarkers for acute exacerbations of COPD (AECOPD). Fecal samples were collected from 30 patients with stable COPD, 30 patients with AECOPD, and 10 healthy individuals. Fecal microbiological profiles were analyzed using 16S rRNA gene sequencing. The results showed a distinct difference in the bacterial community composition between the AECOPD, COPD, and healthy control groups. The COPD and AECOPD groups had higher levels of Firmicutes but lower levels of Bacteroidetes compared to the healthy control group at the phylum level. At the genus level, there was an increased abundance of Lachnoclostridium, Alistipes, Streptococcus, and Prevotella in COPD and AECOPD patients. Increasing levels of Lachnoclostridium and Prevotella may indicate an acute exacerbation of COPD. This study identified specific microbial biomarkers associated with AECOPD and characterized the composition of gut microbiota in patients with AECOPD.

Rhizosphere enrichment and crop utilization of selenium and metals in typical permian soils of Enshi.

Enshi, China, is renowned as "Selenium(Se) Capital" where widely distributed soils derived from Permian parent rocks are notably rich in Se, as well as metals, particularly cadmium(Cd). However, the soil enrichment and crop uptake of Se and metals in these high-Se and high-Cd areas are not well understood. To propose the optimal crop planting plan to ensure the safety of agricultural products, we investigated the soils and corresponding typical crops (rice, tea, and maize). The results showed significant soil enrichment of elements, with average contents (mg/kg) as follows: Cr (185), Zn (126), Cu (58.8), Pb (31.1), As (15.7), Se (6.85), Cd (5.41), and Hg (0.211). All soil Se contents were above 0.4 mg/kg, indicating Se-rich soils. Se primarily existed in an organic-bound form, accounting for an average proportion of 61.3%, while Cd was mainly exchangeable, with an average of 62.5%. Cd exhibited higher activity according to the Relative Index of Activity (RIA). Nemerow single-factor index analysis confirmed significant soil contamination, with Cd showing the highest level, followed by Cr and Cu, while Pb had the lowest level. Tea exhibited a high Se rich ratio (82.0%) without exceeding the Cd standard. In contrast, corn and rice had relatively lower Se-rich ratios (42.0% and 51.5% respectively) and high rates of Cd exceeding the standard, at 49.0% and 61.0% respectively. Canonical analysis revealed that rice was more influenced by soil factors related to Se and Cd compared to maize and tea crops. Therefore, tea cultivation in the Enshi Permian soil area is recommended for safe crop production. This study provides insights into the enrichment, fractionation, and bioavailability of soil Se, Cd, and other metals in the high-Se and high-Cd areas of permian stratas in Enshi, offering a scientific basis for selecting local food crops and producing safe Se-rich agricultural products in the region.

Applying Red Mud in Cadmium Contamination Remediation: A Scoping Review.

Red mud is an industrial solid waste rarely utilized and often disposed of in landfills, resulting in resource waste and environmental pollution. However, due to its high pH and abundance of iron and aluminum oxides and hydroxides, red mud has excellent adsorption properties which can effectively remove heavy metals through ion exchange, adsorption, and precipitation. Therefore, red mud is a valuable resource rather than a waste byproduct. In recent years, red mud has been increasingly studied for its potential in wastewater treatment and soil improvement. Red mud can effectively reduce the migration and impact of heavy metals in soils and water bodies. This paper reviews the research results from using red mud to mitigate cadmium pollution in water bodies and soils, discusses the environmental risks of red mud, and proposes key research directions for the future management of red mud in cadmium-contaminated environments.

A spatial transcriptome map of the developing maize ear.

A comprehensive understanding of inflorescence development is crucial for crop genetic improvement, as inflorescence meristems give rise to reproductive organs and determine grain yield. However, dissecting inflorescence development at the cellular level has been challenging owing to a lack of specific marker genes to distinguish among cell types, particularly in different types of meristems that are vital for organ formation. In this study, we used spatial enhanced resolution omics-sequencing (Stereo-seq) to construct a precise spatial transcriptome map of the developing maize ear primordium, identifying 12 cell types, including 4 newly defined cell types found mainly in the inflorescence meristem. By extracting the meristem components for detailed clustering, we identified three subtypes of meristem and validated two MADS-box genes that were specifically expressed at the apex of determinate meristems and involved in stem cell determinacy. Furthermore, by integrating single-cell RNA transcriptomes, we identified a series of spatially specific networks and hub genes that may provide new insights into the formation of different tissues. In summary, this study provides a valuable resource for research on cereal inflorescence development, offering new clues for yield improvement.

Constructed Rice Tracers Identify the Major Virulent Transcription Activator-Like Effectors of the Bacterial Leaf Blight Pathogen.

Xanthomonas oryzae pv. oryzae (Xoo) injects major transcription activator-like effectors (TALEs) into plant cells to activate susceptibility (S) genes for promoting bacterial leaf blight in rice. Numerous resistance (R) genes have been used to construct differential cultivars of rice to identify races of Xoo, but the S genes were rarely considered. Different edited lines of rice cv. Kitaake were constructed using CRISPR/Cas9 gene-editing, including single, double and triple edits in the effector-binding elements (EBEs) located in the promoters of rice S genes OsSWEET11a, OsSWEET13 and OsSWEET14. The near-isogenic lines (NILs) were used as tracers to detect major TALEs (PthXo1, PthXo2, PthXo3 and their variants) in 50 Xoo strains. The pathotypes produced on the tracers determined six major TALE types in the 50 Xoo strains. The presence of the major TALEs in Xoo strains was consistent with the expression of S genes in the tracers, and it was also by known genome sequences. The EBE editing had little effect on agronomic traits, which was conducive to balancing yield and resistance. The rice-tracers generated here provide a valuable tool to track major TALEs of Xoo in Asia which then shows what rice cultivars are needed to combat Xoo in the field.

Transcriptional Activator UvXlnR Is Required for Conidiation and Pathogenicity of Rice False Smut Fungus Ustilaginoidea virens.

Transcription factors play critical roles in diverse biological processes in fungi. XlnR, identified as a transcriptional activator that regulates the expression of the extracellular xylanase genes in fungi, has not been extensively studied for its function in fungal development and pathogenicity in rice false smut fungus Ustilaginoidea virens. In this study, we characterized UvXlnR in U. virens and established that the full-length, N-terminal, and C-terminal forms have the ability to activate transcription. The study further demonstrated that UvXlnR plays crucial roles in various aspects of U. virens biology. Deletion of UvXlnR affected growth, conidiation, and stress response. UvXlnR mutants also exhibited reduced pathogenicity, which could be partially attributed to the reduced expression of xylanolytic genes and extracellular xylanase activity of U. virens during the infection process. Our results indicate that UvXlnR is involved in regulating growth, conidiation, stress response, and pathogenicity.

Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)-T cell therapy in patients with hematological malignancy.

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.

Tal6b/AvrXa27A, a hidden TALE targeting the susceptibility gene OsSWEET11a and the resistance gene Xa27 in rice.

Xanthomonas oryzae pv. oryzae (Xoo) secretes transcription activator-like effectors (TALEs) to activate rice susceptibility (S) genes, causing bacterial blight (BB), as well as resistance (R) genes, leading to defense against BB. This activation follows a gene-for-gene paradigm that results in an arms race between the TALE of the pathogen and effector-binding elements (EBEs) in the promoters of host genes. In this study, we characterized a novel TALE, designated Tal6b/AvrXa27A, that activates the rice S gene OsSWEET11a and the rice R gene Xa27. Tal6b/AvrXa27A is a member of the AvrXa27/TalAO class and contains 16 repeat variable diresidues (RVDs); one RVD is altered and one is deleted in Tal6b/AvrXa27A compared with AvrXa27, a known avirulence (avr) effector of Xa27. Tal6b/AvrXa27A can transcriptionally activate the expression of Xa27 and OsSWEET11a via EBEs in their corresponding promoters, leading to effector-triggered immunity and susceptibility, respectively. The 16 RVDs in Tal6b/AvrXa27A have no obvious similarity to the 24 RVDs in the effector PthXo1, but EBETal6b and EBEPthXo1 are overlapped in the OsSWEET11a promoter. Tal6b/AvrXa27A is prevalent among Asian Xoo isolates, but PthXo1 has only been reported in the Philippine strain PXO99A. Genome editing of EBETal6b in the OsSWEET11a promoter further confirmed the requirement for OsSWEET11a expression in Tal6b/AvrXa27A-dependent susceptibility to Xoo. Moreover, Tal6b/AvrXa27A resulted in higher transcription of Xa27 than of OsSWEET11a, which led to a strong, rapid resistance response that blocked disease development. These findings suggest that Tal6b/AvrXa27A has a dual function: triggering resistance by activating Xa27 gene expression as an avirulence factor and inducing transcription of the S gene OsSWEET11a, resulting in virulence. Intriguingly, Tal6b/AvrXa27A, but not AvrXa27, can bind to the promoter of OsSWEET11a. The underlying recognition mechanism for this binding remains unclear but appears to deviate from the currently accepted TALE code.

Geochemical relationship and profile distribution of Selenium and Cadmium in typical Selenium-enriched areas in Enshi.

Selenium (Se) is an essential nutrient element for humans, and Se-enriched products are gaining popularity due to their health benefits. However, Enshi, a region in China naturally rich in Se, a high background value of cadmium (Cd) is discovered, which severely impacts local Se-enriched agriculture. Therefore, it is crucial to explore the geochemical relationship between Se and Cd. In this study, we analyzed soil profiles and parent rocks of different geological ages from Enshi to investigate the accumulation and distribution of Se and Cd. The ratio of redox sensitive elements and the multivariate statistical analysis, along with XRD and XPS analysis, were utilized to investigate the correlated relationship between Se and Cd and the underlying geochemical mechanisms. The results showed that average Se and Cd contents in rocks were 1.67 and 0.32 mg/kg. Se and Cd levels reached highest at Permian in rocks of different geological ages, which may be related to the Permian Dongwu movement near the study area. The highest migration rate of Cd and Se from rock to soil was 12 and 1.5 times. The soil Se and Cd fractions were mostly in bound states, with the largest fraction of Se being organic-bound at an average of 45.9%. The reducible and the residue state accounted for the largest proportion in the Cd fractions, with an average of 40.6% and 25.6%. Redox-sensitive element ratios indicate a reducing forming environment of deep sediments in the Permian strata. Furthermore, the correlation and PCA analysis revealed highly significant positive correlations between Se, Cd, V and Cr, suggesting that the sources of Se and Cd were closely related to volcanic and biological activities. In conclusion, a strong geochemical relationship was observed between Se and Cd. And as a result, metal pollution must be closely monitored during the production of Se-enriched agriculture in Se-enriched regions.

UvATG6 Interacts with BAX Inhibitor 1 Proteins and Plays Critical Roles in Growth, Conidiation, and Virulence in Ustilaginoidea virens.

Autophagy and apoptosis are evolutionarily conserved catabolic processes involved in regulating development and cellular homeostasis. Bax inhibitor 1 (BI-1) and autophagy protein 6 (ATG6) perform essential functions in these roles, such as cellular differentiation and virulence in various filamentous fungi. However, the functions of ATG6 and BI-1 proteins in development and virulence in the rice false smut fungus Ustilaginoidea virens are still poorly understood. In this study, UvATG6 was characterized in U. virens. The deletion of UvATG6 almost abolished autophagy in U. virens and reduced growth, conidial production and germination, and virulence. Stress tolerance assays showed that UvATG6 mutants were sensitive to hyperosmotic, salt, and cell wall integrity stresses but were insensitive to oxidative stress. Furthermore, we found that UvATG6 interacted with UvBI-1 or UvBI-1b and suppressed Bax-induced cell death. We previously found that UvBI-1 could suppress Bax-induced cell death and was a negative regulator of mycelial growth and conidiation. Unlike UvBI-1, UvBI-1b could not suppress cell death. UvBI-1b-deleted mutants exhibited decreased growth and conidiation, while the UvBI-1 and UvBI-1b double deletion reduced the phenotype, indicating that UvBI-1 and UvBI-1b antagonistically regulate mycelial growth and conidiation. In addition, the UvBI-1b and double mutants exhibited decreased virulence. Our results provide evidence of the cross talk of autophagy and apoptosis in U. virens and give clues for studying other phytopathogenic fungi. IMPORTANCE Ustilaginoidea virens causes destructive panicle disease in rice, significantly threatening agricultural production. UvATG6 is required for autophagy and contributes to growth, conidiation, and virulence in U. virens. Additionally, it interacts with the Bax inhibitor 1 proteins UvBI-1 and UvBI-1b. UvBI-1 suppresses cell death induced by Bax, unlike UvBI-1b. UvBI-1 negatively regulates growth and conidiation, while UvBI-1b is required for these phenotypes. These results indicate that UvBI-1 and UvBI-1b may antagonistically regulate growth and conidiation. In addition, both of them contribute to virulence. Additionally, our results suggest cross talk between autophagy and apoptosis, contributing to the development, adaptability, and virulence of U. virens.

Inhibition of castration-resistant prostate cancer growth by genistein through suppression of AKR1C3.

Background: Prostate cancer is the second leading cause of cancer-related death among males in America. The patients' survival time is significantly reduced after prostate cancer develops into castration-resistant prostate cancer (CRPC). It has been reported that AKR1C3 is involved in this progression, and that its abnormal expression is directly correlated with the degree of CRPC malignancy. Genistein is one of the active components of soy isoflavones, and many studies have suggested that it has a better inhibitory effect on CRPC. Objective: This study aimed to investigate the antitumor effect of genistein on CRPC and the potential mechanism of action. Design: A xenograft tumor mouse model established with 22RV1 cells was divided into the experimental group and the control group, and the former was given 100 mg/kg.bw/day of genistein, with 22RV1, VCaP, and RWPE-1 cells cultured in a hormone-free serum environment and treated with different concentrations of genistein (0, 12.5, 25, 50, and 100 µmol/L) for 48 h. Molecular docking was used to elucidate the molecular interactions between genistein and AKR1C3. Results: Genistein inhibits CRPC cell proliferation and in vivo tumorigenesis. The western blot analysis confirmed that the genistein significantly inhibited prostate-specific antigen production in a dose-dependent manner. In further results, AKR1C3 expression was decreased in both the xenograft tumor tissues and the CRPC cell lines following genistein gavage feeding compared to the control group, with the reduction becoming more obvious as the concentration of genistein was increased. When the genistein was combined with AKR1C3 small interfering ribonucleic acid and an AKR1C3 inhibitor (ASP-9521), the inhibitory effect on the AKR1C3 was more pronounced. In addition, the molecular docking results suggested that the genistein had a strong affinity with the AKR1C3, and that it could be a promising AKR1C3 inhibitor. Conclusion: Genistein inhibits the progression of CRPC via the suppression of AKR1C3.

Genome sequencing reveals evidence of adaptive variation in the genus Zea.

Maize is a globally valuable commodity and one of the most extensively studied genetic model organisms. However, we know surprisingly little about the extent and potential utility of the genetic variation found in wild relatives of maize. Here, we characterize a high-density genomic variation map from 744 genomes encompassing maize and all wild taxa of the genus Zea, identifying over 70 million single-nucleotide polymorphisms. The variation map reveals evidence of selection within taxa displaying novel adaptations. We focus on adaptive alleles in highland teosinte and temperate maize, highlighting the key role of flowering-time-related pathways in their adaptation. To show the utility of variants in these data, we generate mutant alleles for two flowering-time candidate genes. This work provides an extensive sampling of the genetic diversity of Zea, resolving questions on evolution and identifying adaptive variants for direct use in modern breeding.

Three types of genes underlying the Gametophyte factor1 locus cause unilateral cross incompatibility in maize.

Unilateral cross incompatibility (UCI) occurs between popcorn and dent corn, and represents a critical step towards speciation. It has been reported that ZmGa1P, encoding a pectin methylesterase (PME), is a male determinant of the Ga1 locus. However, the female determinant and the genetic relationship between male and female determinants at this locus are unclear. Here, we report three different types, a total of seven linked genes underlying the Ga1 locus, which control UCI phenotype by independently affecting pollen tube growth in both antagonistic and synergistic manners. These include five pollen-expressed PME genes (ZmGa1Ps-m), a silk-expressed PME gene (ZmPME3), and another silk-expressed gene (ZmPRP3), encoding a pathogenesis-related (PR) proteins. ZmGa1Ps-m confer pollen compatibility. Presence of ZmPME3 causes silk to reject incompatible pollen. ZmPRP3 promotes incompatibility pollen tube growth and thereby breaks the blocking effect of ZmPME3. In addition, evolutionary genomics analyses suggest that the divergence of the Ga1 locus existed before maize domestication and continued during breeding improvement. The knowledge gained here deepen our understanding of the complex regulation of cross incompatibility.

[Heavy Metal Pollution Characteristics and Risk Assessment of Golden Snub-nosed Monkey (Rhinopithecus roxellana) Habitat in Shennongjia Mountains].

The golden snub-nosed monkey is one of the most endangered animal species endemic to China. In order to explore the characteristics and health risks of golden snub-nosed monkeys exposed to heavy metals, we collected the plant food sources, soil, and water samples from the golden snub-nosed monkey habitat in the Shennongjia Mountains; examined the contents of seven heavy metals (Cu, Zn, Pb, Cd, Cr, Ni, and As); and adopted the comprehensive pollution index, potential ecological risk index, and Nemerow index to evaluate pollutants in the water, soil, and food plants. At the same time, the Target Hazard Quotient method was used to assess heavy metals in the food plants. The results showed that the heavy metal concentration of the habitat water was 0.004-1.220 µg·L-1. The water comprehensive pollution index showed that the habitat water was safe. In addition, the ω(Cd)(0.162-0.822 mg·kg-1) in the soil was 2.71 times the background value of the soil in Hubei province, indicating a moderate risk of ecological harm. The over-standard rates of Pb, Cd, Cr, and Ni in food plants were 29%, 29%, 18%, and 35%, respectively; the pollution indexes of lichen and bark were 6.038 and 7.709, which were at a heavy pollution level; and the pollution indexes of Abies fragesii and Vicia cracca were 2.716 and 2.034, which indicated a moderately polluted level. The rest of the plants were at a safe level. Our health risk analysis showed that the risk of lichen and bark were higher than that of leaves, followed by fruits. Among the seven metals, As most threatened the health of the golden snub-nosed monkeys (THQ>1). In general, heavy metals had polluted the habitats of the golden snub-nosed monkeys in the Shennongjia Mountains, and we are certain that the heavy metal pollution was associated with human activities. Thus, human activities in the Shennongjia Mountains should be reasonably restricted in the future. Our results can provide scientific support for the population conservation of golden snub-nosed monkeys in China and provide research samples in the health risk valuation of heavy metals in endangered animals through food plants.

Human Umbilical Cord Mesenchymal Stem Cells to Treat Neuromyelitis Optica Spectrum Disorder (hUC-MSC-NMOSD): A Study Protocol for a Prospective, Multicenter, Randomized, Placebo-Controlled Clinical Trial.

Background: Neuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating NMOSD. Methods: The trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC-MSCs. Patients will be treated with three different doses of hUC-MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years. Discussion: Although hUC-MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC-MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC-MSC in treating NMOSD and might be able to determine the optimal dose of hUC-MSC for NMOSD patients. Trial registration: The study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

Sustained Impact of the Philadelphia Beverage Tax on Beverage Prices and Sales Over 2 Years.

INTRODUCTION: It is unclear whether changes in beverage price and sales after beverage tax implementation can be sustained long term. This study aims to quantify the changes in beverage prices and sales in large retailers 2 years after the implementation of the 1.5 cents per ounce Philadelphia beverage tax. METHODS: Data on price and volume sales of beverages and potential food substitutes were collected from 109 supermarkets, 45 mass merchandizers, and 350 pharmacies in Philadelphia, Baltimore (control), and Pennsylvania ZIP codes bordering Philadelphia (to investigate potential cross-border shopping for tax avoidance). Difference-in-differences analyses compared beverage prices and volume sales in the year before tax implementation (2016) to 2 years after (2018). Data were analyzed in 2020-2021. RESULTS: Difference-in-differences analyses found that after tax implementation, taxed beverage prices in Philadelphia increased by 1.02 cents per ounce (95% CI=0.94, 1.11; 68% pass through), and taxed beverage volume sales in stores decreased by 50% (95% CI=36%, 61%). After accounting for cross-border shopping, taxed beverage volume sales decreased in Philadelphia by 35% in 2018. Volume sales of nontaxed beverages did not change after tax implementation (difference-in-differences=4%, 95% CI= -3%, 12%). Volume sales of nontaxed beverage concentrates increased on average by 34% (95% CI=19%, 51%), but there was no evidence of substitution to high-calorie foods. CONCLUSIONS: There was a large reduction in taxed beverage volume sales 2 years after Philadelphia tax implementation, even after accounting for cross-border shopping. Increases in nontaxed beverage concentrate sales likely partially offset this decline, but there was no evidence of post-tax food substitution.