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Introduction: Depression is a common comorbidity in Parkinson's Disease (PD) and treatment of depression can significantly support PD management. Zishen pingchan granules (ZPG), a traditional Chinese herbal formula, may help ameliorate depressive symptoms in PD patients. However, the molecular mechanisms underlying the effects of ZPG remain unclear. This study aimed to investigate the impact of ZPG on serum levels of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in PD patients with depression. Methods: Eighty PD patients treated with pramipexole but still experiencing mild to moderate depression symptoms were randomly allocated to a group receiving 12-week ZPG treatment (n = 40) or placebo (n = 40). The Hamilton Depression Scale 17 items (HAM-D-17) was utilized to evaluate changes in depressive symptoms from baseline over 12 weeks, while the Unified Parkinson's Disease Rating Scales (UPDRS) part 3 was employed to assess changes in motor symptoms over the same duration. Serum levels of BDNF, IL-1β, IL-6, CRP, and TNF-α were measured at baseline and post-treatment. Results: Seventy-one participants completed the study. Following treatment, both groups showed significantly reduced HAMD scores. The placebo group demonstrated a decrease in BDNF levels, while the ZPG group showed an increase in IL-6 levels post-treatment. In the examination of the group-time interaction, the ZPG group exhibited a greater decrease in HAMD scores and increase in IL-6 levels compared to the placebo group. Conversely, the placebo group showed a greater decrease in BDNF levels compared to the ZPG group. However, no significant group differences were observed in UPDRS part 3 change scores or serum levels of IL-1β, CRP, or TNF-α change from baseline. Conclusion: ZPG may potentially ameliorate depressive symptoms in PD patients, with the potential mechanism involving mitigation of reductions in serum BDNF level and an increase in IL-6 level.

Background: Presently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD — particularly in the newly diagnosed drug-naïve phase — may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations. Methods: We recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age- and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems. Results: GBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p

Abstract Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

It is a challenge to design an effective algorithm utilizing problem features in automated test case generation for path coverage (ATCG-PC). A feature of ATCG-PC “similar paths are usually executed by similar test cases” was touched by a few scholars and can be further exploited to design more effective algorithms. Inspired by this feature, this paper proposes a two-stage local search strategy, denoted dual scatter search (DS) strategy, which concatenates two improved scatter search strategies with different search behaviors. The first stage aims to fully exploit the discovered test cases to search for desired test cases, and the latter stage aims to mine the unexploited areas of the first stage via using less computational overhead. Then, a backtracking search optimization algorithm with dual scatter search strategy (BSA-DS) is proposed, which incorporates DS strategy into the backtracking search optimization algorithm (BSA) with strong exploration capability. BSA is first introduced into the field of ATCG-PC. The performance of BSA-DS and some state-of-the-art algorithms is tested on twelve popular benchmark programs. Experimental studies demonstrate that BSA-DS achieves the highest path coverage with the fewest test cases and running time on at least eight out of the twelve programs.

IntroductionRituximab (RTX) showed good efficacy and safety for patients with myasthenia gravis. However, the percentage of peripheral CD20+ B cell may be absent for years after low dose of RTX treatment. Persistent hypogammaglobulinemia and opportunistic infection may occur in patients under treatment of RTX with thymoma relapse.Case representationWe report a case of refractory myasthenia gravis. After two doses of 100 mg rituximab, the patient developed transient neutropenia. The peripheral blood CD20+ B cell percentage was 0 more than 3 years. Eighteen months later, the patient's symptoms relapsed with thymoma recurred. She had persistent hypogammaglobulinemia and multiple opportunistic infections.ConclusionIn MG patient under B cell depletion therapy had thymoma relapse, Good's syndrome may induce prolonged B cell depletion, hypogammaglobulinemia and opportunistic infections.

ObjectiveVariants in the glucocerebrosidase (GBA) gene are the most common and significant risk factor for Parkinson’s disease (PD). However, the impact of GBA variants on PD disease progression in the Chinese population remains unclear. This study aimed to explore the significance of GBA status on motor and cognitive impairment in a longitudinal cohort of Chinese patients with PD.MethodsThe entire GBA gene was screened by long-range polymerase chain reaction (LR-PCR) and next generation sequencing (NGS). A total of 43 GBA-related PD (GBA-PD) and 246 non-GBA-mutated PD (NM-PD) patients with complete clinical data at baseline and at least one follow-up were recruited for this study. The associations of GBA genotype with rate of motor and cognitive decline, as measured by Unified PD Rating Scale (UPDRS) motor and Montreal Cognitive Assessment (MoCA), were assessed by linear mixed-effect models.ResultsThe estimated (standard error, SE) UPDRS motor [2.25 (0.38) points/year] and MoCA [−0.53 (0.11) points/year] progression rates in the GBA-PD group were significantly faster than those in the NM-PD group [1.35 (0.19); −0.29 (0.04) points/year; respectively]. In addition, the GBA-PD group showed significantly faster estimated (SE) bradykinesia [1.04 (0.18) points/year], axial impairment [0.38 (0.07) points/year], and visuospatial/executive [−0.15 (0.03) points/year] progression rates than the NM-PD group [0.62 (0.10); 0.17 (0.04); −0.07 (0.01) points/year; respectively].ConclusionGBA-PD is associated with faster motor and cognitive decline, specifically greater disability in terms of bradykinesia, axial impairment, and visuospatial/executive function. Better understanding of GBA-PD progression may help predict prognosis and improve clinical trial design.

BackgroundDepression in Parkinson’s disease (PD) is identified and diagnosed with behavioral observations and neuropsychological measurements. Due to the large overlaps of depression and PD symptoms in clinical manifestations, it is challenging for neurologists to distinguish and diagnose depression in PD (DPD) in the early clinical stage of PD. The advancement in magnetic resonance imaging (MRI) technology provides potential clinical utility in the diagnosis of DPD. This study aimed to explore the alterations of functional and structural MRI in DPD to produce neuroimaging markers in discriminating DPD from non-depressed PD (NDPD) and healthy controls (HC).MethodsWe recruited 20 DPD, 37 NDPD, and 41 HC matched in age, gender, and education years. The patients’ diagnosis with PD was de novo. The differences in regional homogeneity (ReHo), voxel-wise degree centrality (DC), cortical thickness, cortical gray matter (GM) volumes, and subcortical GM volumes among these groups were detected, and the relationship between altered indicators and depression was analyzed. Moreover, the receiver operating characteristic (ROC) analysis was performed to assess the diagnostic efficacy of altered indicators for DPD.ResultsCompared to NDPD and HC, DPD showed significantly increased ReHo in left dorsolateral superior frontal gyrus (DSFG) and DC in left inferior temporal gyrus (ITG), and decreased GM volumes in left temporal lobe and right Amygdala. Among these altered indicators, ReHo value in left DSFG and DC values in left ITG and left DSFG were significantly correlated with the severity of depression in PD patients. Comparing DPD and NDPD, the ROC analysis revealed a better area under the curve value for the combination of ReHo value in left DSFG and DC value in left ITG, followed by each independent indicator. However, the difference is not statistically significant.ConclusionThis study demonstrates that both functional and structural impairments are present in DPD. Among them, ReHo value of left DSFG and DC value of left ITG are equally well suited for the diagnosis and differential diagnosis of DPD, with a combination of them being slightly preferable. The multimodal MRI technique represents a promising approach for the classification of subjects with PD.

BackgroundGenetic factors play an important role in the pathogenesis of early-onset Parkinson’s disease (EOPD). To date, more than 20 pathogenic genes associated with Parkinson’s disease (PD) have been identified. This study aims to explore the mutation spectrum of EOPD and the clinical characteristics of mutation carriers in eastern China.MethodsWe recruited 155 unrelated EOPD patients, including 8 familial and 147 sporadic EOPD (age at onset ≤ 50 years). Overall, 24 known PD-associated genes were detected by whole exome sequencing and multiplex ligation-dependent probe amplification (MLPA) from patient samples. The genetic and clinical characteristics of pathogenic/likely pathogenic (P/LP) loci in this cohort were analyzed.ResultsOverall, 14 (9.03%) patients were detected with P/LP variants distributed in seven genes. The most frequent mutation occurred in PRKN (7/155, 4.52%), followed by LRRK2 (2/155, 1.29%), SNCA, CHCHD2, TMEM230, DNAJC13 and PLA2G6 (1/155, 0.64%, respectively). Exon rearrangement mutations accounted for 57.9% (11/19) of all mutations in PRKN. Four novel variants were detected: c.14T > C (p.M5T) in SNCA, c.297C > A (p.Y99X) in CHCHD2, c.2578C > T (p.R860C) in DNAJC13 and c.4C > T (p.Q2X) in TMEM230. We found the first case of LRRK2 c.6055G > A (p.G2019S) mutation in Chinese population. The median onset age of patients with P/LP mutations in autosomal recessive genes (PRKN and PLA2G6) was about 18.0 years earlier than patients without mutation. The proportion of patients with mutations were 63.64%, 27.03% and 9.68% when patients were stratified according to the age of onset at ≤ 30, ≤ 40 and ≤ 50 years, respectively.ConclusionEarly-onset Parkinson’s disease patients from eastern China present a regional specific mutation spectrum. Analysis of larger patient cohorts is required to support these findings, and mechanistic studies of the four novel missense/non-sense mutations will clarify their role in the pathogenicity of EOPD.

Hydrolysis of ZIF-8 in water becomes a key barrier to improving the electrochemical performance of ZIF-derived catalysts. In this paper, dopamine is used to inhibit ZIF-8 hydrolysis. The obtained Fe0.1-NC NPs catalysts exhibit excellent electrochemical activity with a half-wave potential of 0.834 V in 0.1 M KOH electrolyte and satisfactory stability and methanol tolerance. Physical and chemical characterizations suggest that its excellent electrochemical performance is ascribed to the hierarchical porous structure and the synergistic effect of Fe-NX active sites and Fe3O4 nanoparticles. The synthesis solvent of the catalysts is aqueous solution, which provides the possibility for large-scale production.

BackgroundDepression, one of the most frequent non-motor symptoms in Parkinson’s disease (PD), was proposed to be related to neural network dysfunction in advanced PD patients. However, the underlying mechanisms in the early stage remain unclear. The study was aimed to explore the alterations of large-scale neural networks in de novo PD patients with depression.MethodsWe performed independent component analysis (ICA) on the data of resting-state functional magnetic resonance imaging from 21 de novo PD patients with depression (dPD), 34 de novo PD patients without depression (ndPD), and 43 healthy controls (HCs) to extract functional networks. Intranetwork and internetwork connectivity was calculated for comparison between groups, correlation analysis, and predicting the occurrence of depression in PD.ResultsWe observed an ordered decrease of connectivity among groups within the ventral attention network (VAN) (dPD < ndPD < HCs), mainly located in the left middle temporal cortex. Besides, dPD patients exhibited hypoconnectivity between the auditory network (AUD) and default mode network (DMN) or VAN compared to ndPD patients or healthy controls. Correlation analysis revealed that depression severity was negatively correlated with connectivity value within VAN and positively correlated with the connectivity value of AUD-VAN in dPD patients, respectively. Further analysis showed that the area under the curve (AUC) for dPD prediction was 0.863 when combining the intranetwork connectivity in VAN and internetwork connectivity in AUD-DMN and AUD-VAN.ConclusionOur results demonstrated that early dPD may be associated with abnormality of attention bias and especially auditory attention processing. Altered neural network connectivity is expected to be a potential neuroimaging biomarker to predict depression in PD.

BackgroundDepression is one of the most prevalent and disturbing non-motor symptoms in Parkinson’s disease (PD), with few dynamic functional connectivity (dFC) features measured in previous studies. Our aim was to investigate the alterations of the dynamics in de novo patients with PD with depression (dPD).MethodsWe performed dFC analysis on the data of resting-state functional MRI from 21 de novo dPD, 34 de novo patients with PD without depression (ndPD), and 43 healthy controls (HCs). Group independent component analysis, a sliding window approach, followed by k-means clustering were conducted to assess functional connectivity states (which represented highly structured connectivity patterns reoccurring over time) and temporal properties for comparison between groups. We further performed dynamic graph-theoretical analysis to examine the variability of topological metrics.ResultsFour distinct functional connectivity states were clustered via dFC analysis. Compared to patients with ndPD and HCs, patients with dPD showed increased fractional time and mean dwell time in state 2, characterized by default mode network (DMN)-dominated and cognitive executive network (CEN)-disconnected patterns. Besides, compared to HCs, patients with dPD and patients with ndPD both showed weaker dynamic connectivity within the sensorimotor network (SMN) in state 4, a regionally densely connected state. We additionally observed that patients with dPD presented less variability in the local efficiency of the network.ConclusionsOur study demonstrated that altered network connection over time, mainly involving the DMN and CEN, with abnormal dynamic graph properties, may contribute to the presence of depression in patients with PD.

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.

Circulating microRNAs (miRNAs) have been proposed to be accessible biomarkers for Parkinson’s disease (PD). However, there is a lack of known miRNAs that can serve as biomarkers for prodromal PD (pPD). We previously identified that miR-31 and miR-214 were dysregulated in PD. The aim of this study was to explore the roles of miR-31 and miR-214 in pPD. We recruited 25 pPD patients, 20 patients with de novo PD (dnPD), 24 advanced PD (aPD) patients and 21 controls. Next, we investigated the expression of miR-31 and miR-214. Compared to controls, miR-214 was found to be significantly upregulated in pPD patients while miR-31 was significantly upregulated in aPD patients. In addition, the expression of miR-214 was lower in aPD patients compared to both dnPD or pPD patients, while the expression of miR-31 was higher in aPD patients compared to dnPD patients. In order to predict pPD via miRNA expression, the receiver operating characteristic curve was constructed and the area under curve (AUC) was calculated. For pPD prediction by miR-214, the AUC was 0.756. The optimal cut-off value of miR-214 was 0.1962, and the sensitivity and specificity were 72.0% and 76.2%, respectively. On the other hand, the AUC for aPD detection by miR-31 was 0.744. The optimal cut-off value for miR-31 was 0.0148, with a sensitivity of 87.5% and a specificity of 71.4%. In conclusion, miR-214 can distinguish pPD patients from controls and may be used as a potential biomarker for pPD diagnosis.

ObjectivePatients with Parkinson’s disease (PD) are commonly classified into subtypes based on motor symptoms. The aims of the present study were to determine the consistency between PD motor subtypes, to assess the stability of PD motor subtypes over time, and to explore the variables influencing PD motor subtype stability.MethodsThis study was part of a longitudinal study of de novo PD patients at a single center. Based on three different motor subtype classification systems proposed by Jankovic, Schiess, and Kang, patients were respectively categorized as tremor-dominant/indeterminate/postural instability and gait difficulty (TD/indeterminate/PIGD), TDS/mixedS/akinetic-rigidS (ARS), or TDK/mixedK/ARK at baseline evaluation and then re-assessed 1 month later. Demographic and clinical characteristics were recorded at each evaluation. The consistency between subtypes at baseline evaluation was assessed using Cohen’s kappa coefficient (κ). Additional variables were compared between PD subtype groups using the two-sample t-test, Mann–Whitney U-test or Chi-squared test.ResultsOf 283 newly diagnosed, untreated PD patients, 79 were followed up at 1 month. There was fair agreement between the Jankovic, Schiess, and Kang classification systems (κS = 0.383 ± 0.044, κK = 0.360 ± 0.042, κSK = 0.368 ± 0.038). Among the three classification systems, the Schiess classification was the most stable and the Jankovic classification was the most unstable. The non-motor symptoms questionnaire (NMSQuest) scores differed significantly between PD patients with stable and unstable subtypes based on the Jankovic classification (p = 0.008), and patients with a consistent subtype had more severe NMSQuest scores than patients with an inconsistent subtype.ConclusionFair consistency was observed between the Jankovic, Schiess, and Kang classification systems. For the first time, non-motor symptoms (NMSs) scores were found to influence the stability of the TD/indeterminate/PIGD classification. Our findings support combining NMSs with motor symptoms to increase the effectiveness of PD subtypes.

Objective: The aims of this study were to compare the characteristics of three motor subtype classifications in patients with de novo Parkinson's disease (PD) and to find the most suitable motor subtype classification for identifying non-motor symptoms (NMSs).Methods: According to previous studies, a total of 256 patients with de novo PD were classified using the tremor-dominant/mixed/akinetic-rigid (TD/mixed/AR), TD/indeterminate/postural instability and gait disturbance (PIGD), and predominantly TD/predominantly PIGD (p-TD/p-PIGD) classification systems.Results: Among the TD/mixed/AR subgroups, the patients with the AR subtype obtained more severe motor scores than the patients with the TD subtype. Among the TD/indeterminate/PIGD subgroups and between the p-TD and p-PIGD subgroups, the patients with the PIGD/p-PIGD subtype obtained more severe scores related to activities of daily living (ADL), motor and non-motor symptoms, including depression, anxiety, and sleep impairment, than the patients with the TD/p-TD subtype. Furthermore, symptoms in the cardiovascular, gastrointestinal, and miscellaneous domains of the Non-motor Questionnaire (NMSQuest) were more prevalent in the patients with the PIGD/p-PIGD subtypes than the patients with the TD/p-TD subtypes.Conclusions: The PIGD/p-PIGD subtypes had more severe ADL, motor and non-motor symptoms than the TD/p-TD subtypes. We disclosed for the first time that the TD/indeterminate/PIGD classification seems to be the most suitable classification among the three motor subtype classifications for identifying NMSs in PD.

The high price and unsatisfactory stability of Pt-based catalysts for the sluggish oxygen reduction reaction (ORR) severely limit the development of fuel cells and metal-air batteries. Therefore, developing Pt-free electrocatalysts with excellent activities and stabilities is significant. Herein, an efficient Zn/Fe–N–C electrocatalyst is synthesized via a facile one-pot method. Owing to its curved nanosheet structure, appropriate microporous and mesoporous specific surface areas, abundant defects and high Fe–Nx content, Zn/Fe–N–C exhibits remarkable ORR activity and stability in alkaline electrolyte. Its half-wave potential is 0.843 V, which is 10 mV higher than that of Pt/C. Moreover, Zn/Fe–N–C also manifests satisfactory performance in a practical Zn-air battery. Its maximum output power density is 108.5 mW cm ^−2 , which is equivalent to that of Pt/C. In this work, a simple synthesis method for highly active ORR electrocatalyst is provided, which can be implemented for the future design and synthesis of electrocatalysts used in fuel cells and metal-air batteries.

In recent years, air pollution has received serious concerns from researchers, media, and the public sectors, but air pollution from agricultural production activities has not received enough attention. This paper focuses on agricultural air pollution in central China, which is aggravated by the ongoing rural labor migration trend. With a set of panel data released from Hubei and Hunan provinces in China, we adopt the mediating effect model to explore the relationship between rural labor migration and air pollution caused by agricultural activity in China. First, we use the inventory analysis method and principal component analysis method to calculate the comprehensive index of the air pollution of agriculture in 152 counties and districts from Hubei and Hunan provinces, and we empirically test the impact of labor migration on air pollution with a mediating effect model as well as carry out regional heterogeneity analysis on the pollution effect of these two provinces mentioned above. The analysis above indicates that the increase of labor migration has intensified the comprehensive index of air pollution caused by agricultural activity by changing the supply of labor force in the agricultural sector, the budget line of rural residents, and the scale of agricultural production and crop planting structure, but there is a difference in the indirect total effect between the two provinces mentioned above according to our regional heterogeneity analysis. This study is a necessary extension to studies on alleviating and controlling air pollution in China.

The impact of air pollution on human health is becoming increasingly severe, and economic losses are a significant impediment to economic and social development. This paper investigates the impact of air pollutants on the respiratory system and its action mechanism by using information on inpatients with respiratory diseases from two IIIA (highest) hospitals in Wuhan from 2015 to 2019, information on air pollutants, and meteorological data, as well as relevant demographic and economic data in China. This paper describes the specific conditions of air pollutant concentrations and respiratory diseases, quantifies the degree of correlation between the two, and then provides a more comprehensive assessment of the economic losses using descriptive statistical methods, the generalized additive model (GAM), cost of illness approach (COI), and scenario analysis. According to the findings, the economic losses caused by PM2.5, PM10, SO2, NO2, and CO exposure are USD 103.17 million, USD 70.54 million, USD 98.02 million, USD 40.35 million, and USD 142.38 million, for a total of USD 454.46 billion, or approximately 0.20% of Wuhan’s GDP in 2019. If the government tightens control of major air pollutants and meets the WHO-recommended criterion values, the annual evitable economic losses would be approximately USD 69.4 million or approximately 0.03% of Wuhan’s GDP in 2019. As a result, the relevant government departments must strengthen air pollution control to mitigate the impact of air pollution on population health and the associated economic losses.

Food safety is a significant livelihood issue. A thorough comprehensive evaluation index system of food safety is constructed based on two-factor theory from the perspective of solving large social tensions and transforming the economic development pattern. The system has bottom line indicator of hygiene factors and improving indicator of incentive factors. The proposed index system can achieve the integration of appraisal, supervision and management and meet the demand of government, enterprises and the public.

The health and education consequences of school feeding programs have been well established, however, evidence regarding such programs' spillover effects on children's noncognitive skills remains scarce. Using the China Education Panel Survey (CEPS), this study examines the association between the Nutrition Improvement Program (NIP), which provides free school meals to eligible rural students, and children's Big Five noncognitive skills. The results show that the school feeding program significantly improves children's noncognitive outcomes, especially among students who are girls, left behind by parents, non-only-child, have a local hukou, live in low-income households, and have low levels of positive personality traits. Our main findings are robust to a battery of specifications and validity tests. In addition, we further explore the possible mechanisms and find that child health, cognitive skills, peer relationship, family economic status, and parenting behaviours are the potential channels through which participating in the school feeding program positively affects children's noncognitive development. Our findings suggest that school feeding should not only be treated as a nutrition or education scheme, but also as a transfer program that fosters children's development beyond health and academic outcomes. [ABSTRACT FROM AUTHOR]

Plasmin is an important factor affecting the shelf-life quality of milk products, and its hydrolytic activity is regulated by many factors, such as activators, inhibitors, and activator inhibitors. Compared with protease secreted by psychrophilic bacteria, plasmin presents different thermal inactivation parameters and hydrolysis properties; the milk gelation properties induced by the two enzymes, the gelation mechanisms and the methods used to detect the milk hydrolysates are different. Plasmin activity in raw milk is affected by dairy cow breeds, lactation stage, parity, and the number of somatic cells, as well as protease secreted by bacteria. As whey protein, casein and Maillard reaction can affect plasmin structure and substrate recognition by it, heating, membrane filtration, and high pressure processing can affect plasmin activity. In this paper, we summarize the composition and regulatory mechanism of the plasmin system in milk, the mechanism of plasmin-induced age gelation of milk, the factors affecting plasmin activity and the methods used to assay plasmin activity, with the aim to provide a reference for further research on milk plasmin.