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Objective In this study, we explored the effect of fruit and vegetable waste addition on the quality of corn stalk silage. Methods Corn stalks were ensiled 20 days after ear harvesting and mixed with fruit and vegetable waste (FVW) consisting of apple, orange, broccoli, and Chinese cabbage waste as 3% of fresh matter. Fruit waste consisted of solid residue obtained after juicing, and vegetable waste was collected from farms and cut into small pieces (2 to 3 cm). The materials were stored anaerobically in 20-L silo buckets and opened after 60 days of fermentation. Results There were significant differences in dry matter (DM), acid detergent fiber (ADF), neutral detergent fiber (NDF), total digestible nutrient (TDN), and relative feed value (RFV) levels in FVW derived from all tested raw materials (p0.05) and significant decreases in yeast and mold counts (p

Abstract Background Xanthenes and multi-aryl carbon core containing compounds represent different types of complex and condensed architectures that have impressive wide range of pharmacological, industrial and synthetic applications. Moreover, indoles as building blocks were only found in naturally occurring metabolites with di-aryl carbon cores and in chemically synthesized tri-aryl carbon core containing compounds. Up to date, rare xanthenes with indole bearing multicaryl carbon core have been reported in natural or synthetic products. The underlying mechanism of fluorescein-like arthrocolins with tetra-arylmethyl core were synthesized in an engineered Escherichia coli fed with toluquinol remained unclear. Results In this study, the Keio collection of single gene knockout strains of 3901 mutants of E. coli BW25113, together with 14 distinct E. coli strains, was applied to explore the origins of endogenous building blocks and the biogenesis for arthrocolin assemblage. Deficiency in bacterial respiratory and aromatic compound degradation genes ubiX, cydB, sucA and ssuE inhibited the mutant growth fed with toluquinol. Metabolomics of the cultures of 3897 mutants revealed that only disruption of tnaA involving in transforming tryptophan to indole, resulted in absence of arthrocolins. Further media optimization, thermal cell killing and cell free analysis indicated that a non-enzyme reaction was involved in the arthrocolin biosynthesis in E. coli. Evaluation of redox potentials and free radicals suggested that an oxygen-mediated free radical reaction was responsible for arthrocolins formation in E. coli. Regulation of oxygen combined with distinct phenol derivatives as inducer, 31 arylmethyl core containing metabolites including 13 new and 8 biological active, were isolated and characterized. Among them, novel arthrocolins with p-hydroxylbenzene ring from tyrosine were achieved through large scale of aerobic fermentation and elucidated x-ray diffraction analysis. Moreover, most of the known compounds in this study were for the first time synthesized in a microbe instead of chemical synthesis. Through feeding the rat with toluquinol after colonizing the intestines of rat with E. coli, arthrocolins also appeared in the rat blood. Conclusion Our findings provide a mechanistic insight into in vivo synthesis of complex and condensed arthrocolins induced by simple phenols and exploits a quinol based method to generate endogenous aromatic building blocks, as well as a methylidene unit, for the bacteria-facilitated synthesis of multiarylmethanes.

Correctly responding to the arrival of unexpected innovative events can help members of the franchise system rationally formulate their operational strategies and cooperative alliance modes to improve performance, while the exact time of product innovation realization is often unknown. Based on this, the strategic interactions in the business innovation system when foreseeing innovations are considered: the choice of operation strategies and cooperation modes. Using Bellman’s continuum dynamic programming theory to find the optimal strategies and system profits under the three modes of horizontal, non-cooperative and vertical cooperation within the system, the strategic interactions in the franchise system under different cooperation modes are analyzed. It is found that the prediction of innovation events will make the decision makers more active in increasing the input of current strategies, thus maximizing the initiative before the realization of innovations, and the R&D and innovation efforts of franchisors and the local service level of franchisors will increase with the increase of the innovation realization rate and the improvement rate, and the goodwill of franchisors will be improved as a result. Both horizontal and vertical cooperation models can effectively realize the Pareto improvement of the total profit of the franchise system. And the innovation realization rate and upliftment rate positively affect this improvement effect. It is worth noting that the vertical cooperation model is more effective in improving the total system profit and is better in the case of high realization rate-high uplift rate.

Background The emergence of the green supply chain represents a natural evolution from the traditional model. However, this transition has created trust concerns in operational processes. Fortunately, blockchain technology offers a promising solution to address this issue and help businesses overcome related obstacles. As artificial intelligence and blockchain continue to advance, enterprises are increasingly exploring opportunities for green innovation investments, although the optimal timing for successful product innovation can be difficult to predict. Methods The effects of successful innovation on eco-friendly supply chains are analyzed through various factors such as optimal investment strategy, level of blockchain technology, and overall system profit. Differential game theory is used to determine the most effective approach across three alliance modes: horizontal cooperative, non-cooperative, and vertical cooperative. Additionally, the impact of innovation uncertainty on member strategies and alliance selection is thoroughly examined. Results According to the results, predicting the likelihood of innovation realization can influence decision makers to prioritize current profits. Both horizontal and vertical cooperative alliance models can lead to Pareto improvements in total system profit, both before and after innovation success. However, the vertical cooperative alliance model proves to be more effective, especially at higher realization rates. Green suppliers stand to benefit from the vertical cooperative alliance model, as it can enhance their innovative investment strategy, while platform cooperation does not significantly affect their strategy. Platforms, on the other hand, can benefit from the vertical cooperative alliance model, as it can promote their innovative investment strategy and level of blockchain technology.

With the growth of people’s demand for loans, banks and other financial institutions put forward higher requirements for customer credit risk level classification, the purpose is to make better loan decisions and loan amount allocation and reduce the pre-loan risk. This article proposes a Multi-Level Classification based Ensemble and Feature Extractor (MLCEFE) that incorporates the strengths of sampling, feature extraction, and ensemble classification. MLCEFE uses SMOTE + Tomek links to solve the problem of data imbalance and then uses a deep neural network (DNN), auto-encoder (AE), and principal component analysis (PCA) to transform the original variables into higher-level abstract features for feature extraction. Finally, it combined multiple ensemble learners to improve the effect of personal credit risk multi-classification. During performance evaluation, MLCEFE has shown remarkable results in the multi-classification of personal credit risk compared with other classification methods.

In order to maximize personal interests, enterprises have a tendency to choose environmental pollution in exchange for corporate profits, resulting in negative externalities; the Civil Code of the People’s Republic of China imposes legal regulations on the environmental infringement of enterprises in order to achieve the maximization of the use of the allocation of social resources and promote the sustainable development of society. Subsequent judicial interpretations have set a two-fold cap on the amount of punitive damages. However, in cases of extremely serious environmental damage, the two-fold cap on punitive damages for environmental infringement will create the possibility of insufficient compensation. Based on this, this paper analyzes the legal text of China’s punitive damages provisions for environmental infringement and analyzes the interrelationships between enterprises and between enterprises and potential environmental infringement victims in a game analysis. The results of the analysis show that as the amount of punitive damages for environmental infringement increases, the probability of the infringed person filing a lawsuit and that of the enterprise reducing its environmental infringement behavior also increase. In order to promote the cause of China’s sustainable development, this paper puts forward relevant suggestions for the improvement of China’s environmental legal regulation: first, the upper limit of the amount of punitive damages for environmental infringement should be canceled; second, the amount of reasonable punitive damages should be set on the basis of the damages caused by environmental infringement on human beings and the environment; lastly, in the baseline setting of the amount of punitive damages, additional factors need to be taken into account, and the amount of punitive damages should be set for the enterprises with a high degree of maliciousness. Finally, additional factors need to be considered in setting the benchmark for the amount of punitive damages, which should penalize the enterprises causing environmental infringement with a high degree of malice with heavier penalties and, at the same time, penalize the enterprises with a smaller scale of operation and economic strength with lighter penalties.

Abstract Postural abnormalities are common disabling motor complications affecting patients with Parkinson’s disease (PD). We proposed a summary index for postural abnormalities (IPA) based on Kinect depth camera and explored the clinical value of this indicator. Seventy individuals with PD and thirty age-matched healthy controls (HCs) were enrolled. All participants were tested using a Kinect-based system with IPA automatically obtained by algorithms. Significant correlations were detected between IPA and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (r s = 0.369, p = 0.002), MDS-UPDRS-III total score (r s = 0.431, p

Background and purpose: Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment has become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, 10%-30% of NSCLC patients with EGFR sensitive mutation still have primary drug resistance when receiving TKI targeted therapy. Therefore, to study the clinical efficacy of EGFR-TKI and find out its prognostic predictors has important significance for the treatment of advanced NSCLC patients with EGFR sensitive mutation. The purpose of this research was to evaluate the efficacy of icotinib as first-line treatment in patients with EGFR-mutant advanced NSCLC and investigate the prognostic predictors. Methods: A total of 258 stage ⅢB-Ⅳ NSCLC patients with EGFR mutation who were admitted to Fujian Cancer Hospital from January 2016 to November 2017 were selected. One hundred and eighteen advanced NSCLC patients with EGFR mutation were enrolled, and baseline circulating tumor DNA (ctDNA) EGFR-mutant status was determined using the plasma test. All these patients received icotinib 125mg three times a day. The χ2 test was used to compare the differences in clinicopathological characteristics between different EGFR mutation groups. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier survival curve. The log-rank test was used for univariate analysis, and the COX regression model was used for multivariate analysis. Results: The objective response rate (ORR) of 118 patients was 62.7% (95% CI: 53.9%-71.6%), the disease control rate (DCR) was 92.4% (95% CI: 87.5%-97.2%), and the median PFS was 11.3months (95% CI: 9.1-13.5 months), and the median OS was 32.0 months (95% CI: 26.9-37.1 months). No statistically significant difference was found in the clinicopathological characteristics between different EGFR expression types (P>0.05), while the best efficacy between different EGFR mutation groups was significantly different (P=0.040). Univariate analysis showed that EGFR mutation status in plasma ctDNA test was not correlated with PFS and OS of patients (P>0.05). Multivariate analysis showed that baseline lactate dehydrogenase (LDH) expression level, EGFR types, pleural effusion and the best curative effect might be independent factors of PFS. The patient’s N stage, bone metastasis, time to PFS and presence of EGFR T790M mutation might be independent predictors of OS. Conclusion: Icotinib as first-line treatment was effective in EGFR-mutant advanced NSCLC patients. The EGFR mutation status in plasma ctDNA test was not correlated with the clinical efficacy of patients. Bone metastasis was found to be an independent factor of worse prognosis.

Objective To quantify bradykinesia in Parkinson's disease (PD) with a Kinect depth camera-based motion analysis system and to compare PD and healthy control (HC) subjects. Methods Fifty PD patients and twenty-five HCs were recruited. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was used to evaluate the motor symptoms of PD. Kinematic features of five bradykinesia-related motor tasks were collected using Kinect depth camera. Then, kinematic features were correlated with the clinical scales and compared between groups. Results Significant correlations were found between kinematic features and clinical scales ( P

In the original publication [...]

BackgroundDecreased myocardial uptake of 131I-metaiodobenzylguanidine (MIBG) is known to be an important feature to diagnose Parkinson’s disease (PD). However, the diagnosis accuracy of myocardial MIBG scintigraphy alone is often unsatisfying. Recent studies have found that the MIBG uptake of the major salivary glands was reduced in PD patients as well.PurposeTo evaluate the diagnostic value of major salivary gland MIBG scintigraphy in PD, and explore the potential role of myocardial MIBG scintigraphy combined with salivary gland MIBG scintigraphy in distinguishing PD from non-PD (NPD).MethodsThirty-seven subjects were performed with 131I-MIBG scintigraphy. They were classified into the PD group (N = 18) and the NPD group (N = 19), based on clinical diagnostic criteria, DAT PET and 18F-FDG PET imaging findings. Images of salivary glands and myocardium were outlined to calculated the MIBG uptake ratios.ResultsThe combination of left parotid and left submandibular gland early images had a good performance in distinguishing PD from NPD, with sensitivity, specificity, and accuracy of 50.00, 94.74, and 72.37%, respectively. Combining the major salivary gland and myocardial scintigraphy results in the early period showed a good diagnostic value with AUC, sensitivity and specificity of 0.877, 77.78, and 94.74%, respectively. Meanwhile, in the delayed period yield an excellent diagnostic value with AUC, sensitivity and specificity of 0.904, 88.89, and 84.21%, respectively.Conclusion131I-MIBG salivary gland scintigraphy assisted in the diagnosis and differential diagnosis of PD. The combination of major salivary gland and myocardial 131I-MIBG scintigraphy further increased the accuracy of PD diagnosis.

The atmospheric oxidation of dimethyl sulfide affects the Earth’s climate, but the intricate pathways of this complex reaction are still not fully described. Here, the authors use an optimized flash pyrolysis method for gas-phase generation of the methylthio radical to study its O2-oxidation via matrix-isolation spectroscopy, and unambiguously identify two peroxyl radical intermediates.

With the large-scaling and intensification of crude oil reserves, storage tanks are also developed in the direction of large capacity. Hence, it is easy to trigger a chain fire effect in the tank farm once a fire occurs, causing huge economic losses and even casualties. In order to reasonably design the safety distance of large crude oil storage tanks and reduce the heat radiation effect of the firing tank on the adjacent tanks, the fire of the storage tank was numerically simulated with the CFD technology. Meanwhile, the influence of the three factors, including the wind speed, spray intensity and oil burning rate, on the safety distance of large crude oil storage tanks were analyzed by controlling a single variable and designing the orthogonal working conditions. The results show that the three factors ranking in a decreasing order of influence are the spray intensity, wind speed and oil burning rate successively. To reduce the safety distance between the storage tanks, it is recommended to increase the spray intensity of cooling water. Thereby, the research results could provide guidance for the layout design of crude oil reserves.

ObjectivesThis study analyzed the clinical and imaging characteristics of patients with cancer-related cryptogenic stroke (CCS) involving the bilateral anterior and the posterior circulations (three circulations) and evaluate the diagnostic value of clinical and imaging features for patients with cryptogenic stroke involving three circulations (CST).MethodsOf the 12,580 patients with acute ischemic stroke, 148 patients with CST from May 2017 to November 2021 were divided into the cancer group (n = 81) and the non-cancer group (n = 67). Cardiovascular risk factors, diffusion-weighted imaging patterns of cryptogenic stroke, blood routine, coagulation routine, and biochemical routine were compared between the two groups. Multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine associations between the two groups.ResultsCompared with the non-cancer group, the cancer group exhibited higher D-dimer levels (P < 0.001), fibrin degradation product (FDP, P < 0.001), international normalized ratio (INR, P = 0.014), neutrophil to lymphocyte ratio (NLR, P < 0.001), platelets to lymphocyte ratio (PLR, P = 0.001), activated partial thromboplastin time (APTT, P = 0.039), more frequent multiple lesions in three circulations (P < 0.001) and lower lymphocytes (P < 0.001), red blood cells (P < 0.001), and thrombin time (TT, P = 0.034). Furthermore, D-dimer [area under the curve (AUC) = 0.915, P < 0.001)], FDP (AUC = 0.923, P < 0.001), INR (AUC = 0.617, P = 0.014), NLR (AUC = 0.700, P < 0.001), PLR (AUC = 0.658, P = 0.001), and multiple lesions in three circulations (AUC = 0.786, P < 0.001) had potential diagnostic value in cryptogenic stroke. When combining these 6 parameters, the predictive power was improved (AUC = 0.949, P < 0.001).ConclusionCryptogenic stroke involving three circulations with cancer has unique clinical features, and these potential diagnostic indicators could help patients identify CCS earlier.

It is known that, long-distance concrete pipeline transportation often causes pipe blocking accidents. For the problem of pipeline blockage, we have invented a swirl speed-increasing device. In this study, the discrete element method was used to calibrate the parameters of the contact model through the slump bucket experiment, and a discrete element model of horizontal pumping concrete was established. Based on the particle unit, the flow-promoting mechanism of the swirl speed-increasing device was studied, and the effects of the pumping speed, the volume fraction of coarse aggregate and the wind speed output of the device on the movement state of the particles and the flow-promoting distance were analyzed. The results show that the maximum velocity and flow-promoting distance of the particle unit increase with the increase of pumping speed and wind speed, and decrease with the increase of the coarse aggregate volume fraction. When the pumping speed and wind speed are large, the installation distance of the flow promoting device should be increased. When the volume fraction of concrete aggregate is large, the installation distance of the flow promoting device should be shortened. Our swirl speed-increasing device can solve the problem of pumping concrete pipeline blockage. The discrete element model of pumping concrete established in this study can well reflect the motion state of the concrete unit in the pipeline, which verifies the applicability of the discrete element model. The numerical simulation conclusion in this paper can avoid system energy waste and pipeline blockage caused by improper selection of device installation spacing.

BackgroundAxial disturbances are the most disabling symptoms of Parkinson’s disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity.PurposeThe present research aimed to quantify the therapy–response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera.Materials and methodsWe enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman’s correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data.ResultsAll the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P < 0.001), the height of foot lift (P < 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (rs = 0.345, P = 0.022; rs = 0.382, P = 0.010; rs = 0.314, P = 0.038; rs = 0.518, P < 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (β = 0.593, 95% CI = 0.023–1.164, P = 0.042).ConclusionAxial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.

Lean burn combustor can save fuel and reduce pollutant emissions. The exit of the lean burn combustor generates strong swirling flow, which has a significant influence on the heat transfer performance of the downstream turbine. Turbine cooling systems have been designed under uniform inflow in the past, lean burn combustor pose new challenges to the design of cooling systems for downstream turbines. In this paper, the effect of swirling inflow on the film cooling effectiveness on the pressure and suction sides of the turbine was experimentally investigated, and the performance of the cylindrical film hole and water-drop shaped hole and fan shaped hole were compared. The results show that the swirling inflow makes the distribution of film uneven and reduces the average value. The swirling inflow reduces the area averaged cooling effectiveness by 5.5% under design working condition. The expanded film hole can improve the cooling effectiveness under swirling inflow. On the suction side, the fan shaped hole performs better than the water-drop shaped hole. On the pressure side, the water-drop shaped hole performs better than the fan-shaped hole. As for area averaged value, the water-drop shaped hole and fan shaped hole perform 46.6% and 51.5% improvement, respectively, compared with cylindrical hole under design working condition.

Background: Clear cell renal cell carcinoma (ccRCC) is the most frequent and lethal type of kidney cancer. Although differential expression of cyclin-dependent kinase-like 2 (CDKL2) has been reported to be associated with tumor progression in other cancers, its prognostic value, and potential mechanism in patients with ccRCC still remain unknown.Methods: Gene expression analysis was conducted using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and International Cancer Genome Consortium databases. Further, clinicopathologic analysis; Kaplan–Meier survival analysis; weighted gene co-expression network analysis; gene set enrichment analysis; gene ontology enrichment; methylation; and immune infiltration analyses were performed using TCGA-kidney renal clear cell carcinoma profiles. CDKL2 translational levels were analyzed using The Human Protein Atlas database.Results:CDKL2 expression was decreased in ccRCC samples retrieved from the four databases. Gender, survival status, histologic grade, clinical stage, TNM classification, and tumor status were closely related to CDKL2 expression. In addition, CDKL2 downregulation was an independent prognostic factor for poor prognosis in multivariate analysis. Enrichment analyses using multiple tests revealed that CDKL2 is not just closely related to immune response but this association is highly correlated as well. Further, we found that CDKL2 expression was significantly correlated with the infiltration levels of T cell CD4 memory resting; monocytes; macrophages M0, M1, and M2; dendritic cells resting; mast cells resting; plasma cells; T cell CD8; and T cell regulatory.Conclusion: This is the first report to study the expression of CDKL2 in ccRCC, wherein we suggest that decreased CDKL2 expression is closely correlated with poor prognosis in ccRCC. We consider that CDKL2 is a novel and potential prognostic biomarker associated with immune infiltrates in ccRCC.

Wet shotcrete support is the main support method for underground engineering construction at present. The rebound rate is one of the indicators to evaluate the support effect, and a lower rebound rate will improve the construction effect of wet shotcrete. The concrete aggregates available in different regions of China have different particle sizes. To achieve better supporting effect, the discrete element method is used to simulate the spraying process of wet shotcrete. By constructing the nozzle structure and simplifying the concrete structure, the paper establishes the discrete element model of wet shotcrete. Using the above model, the paper analyzes the effects of injection distance and shrinkage angle on the injection rebound rate of concrete with three aggregate sizes of 5∼11 mm, 11∼17 mm, and 17∼25 mm. The optimal construction parameters of concrete with different aggregate particle size ratios were obtained through simulation experiments. The simulation results are highly consistent with the field experimental structure. It is feasible to simulate wet shotcrete spraying process by the discrete element method.

Abstract Difluorothiophosphoryl isocyanate, F2P(S)NCO was characterized with UV/vis, NMR, IR (gas and Ar‐matrix), and Raman (liquid) spectroscopy. Its molecular structure was also established by means of gas electron diffraction (GED) and single crystal X‐ray diffraction (XRD) in the gas phase and solid state, respectively. The analysis of the spectroscopic data and molecular structures is complemented by extensive quantum‐chemical calculations. Theoretically, the Cs symmetric syn‐conformer is predicted to be the most stable conformation. Rotation about the P−N bond requires about 9 kJ mol−1 and the predicted existence of an anti‐conformer is dependent on the quantum‐chemical method used. This syn‐orientation of the isocyanate group is the only one found in the gas phase and contained likewise in the crystal. The overall molecular structure is very similar in gas and solid, despite in the solid state the molecules arrange through intramolecular O⋅⋅⋅F contacts into layers, which are further interconnected by S⋅⋅⋅N, S⋅⋅⋅C and C⋅⋅⋅F contacts. Additionally, the photodecomposition of F2P(S)NCO to form CO, F2P(S)N, and F2PNCO is observed in the solid Ar‐matrix.

Abnormal events involving hidden dangers, near misses and non-casualty accidents are the early warning and signs of serious accidents.Considering the high frequency of such incidents, the accident model was established to identify and correct unsafe factors in such incidents so as to effectively prevent serious accidents.According to the process features and accident characteristics of the tank area, the System Hazard Identification, Prediction and Prevention(SHIPP) model was improved, and the tank area accident model based on safety barriers was built.The cause-consequence relationship model was constructed by combining fault tree and event tree, which were mapped into Bayesian network to characterize uncertainty and conditional dependence.As for new evidence information, probability updating was implemented through Bayesian network update mechanism.Though the empirically learning on the field abnormal event data based on Bayesian theory, the uncertainty of prior probability can be reduced and the dynamic risk prediction of accidents in oil tank area can be implemented.A tank area case was analyzed and the results show that, the probability of material and energy release in the tank area is high, the overall safety performance tends to deteriorate, and the safety inspection and hidden danger investigation should be strengthened.The research results can provide scientific guidance and decision support for risk prediction and accident prevention of large oil tank area.

Gait disturbance is a prototypical feature of Parkinson’s disease (PD), and the quantification of gait using wearable sensors is promising. This study aimed to identify gait impairment in the early and progressive stages of PD according to the Hoehn and Yahr (H–Y) scale. A total of 138 PD patients and 56 healthy controls (HCs) were included in our research. We collected gait parameters using the JiBuEn gait-analysis system. For spatiotemporal gait parameters and kinematic gait parameters, we observed significant differences in stride length (SL), gait velocity, the variability of SL, heel strike angle, and the range of motion (ROM) of the ankle, knee, and hip joints between HCs and PD patients in H–Y Ⅰ-Ⅱ. The changes worsened with the progression of PD. The differences in the asymmetry index of the SL and ROM of the hip were found between HCs and patients in H–Y Ⅳ. Additionally, these gait parameters were significantly associated with Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Questionnaire-39. This study demonstrated that gait impairment occurs in the early stage of PD and deteriorates with the progression of the disease. The gait parameters mentioned above may help to detect PD earlier and assess the progression of PD.

Gut microbiota have important implications for health by affecting the metabolism of diet and drugs. However, the specific microbial mediators and their mechanisms in modulating specific key intermediate metabolites from fungal origins still remain largely unclear. Toluquinol, as a key versatile precursor metabolite, is commonly distributed in many fungi, including Penicillium species and their strains for food production. The common 17 gut microbes were cultivated and fed with and without toluquinol. Metabolic analysis revealed that four strains, including the predominant Enterococcus species, could metabolize toluquinol and produce different metabolites. Chemical investigation on large-scale cultures led to isolation of four targeted metabolites and their structures were characterized with NMR, MS, and X-ray diffraction analysis, as four toluquinol derivatives (1–4) through O1/O4-acetyl and C5/C6-methylsulfonyl substitutions, respectively. The four metabolites were first synthesized in living organisms. Further experiments suggested that the rare methylsulfonyl groups in 3–4 were donated from solvent DMSO through Fenton’s reaction. Metabolite 1 displayed the strongest inhibitory effect on cancer cells A549, A2780, and G401 with IC50 values at 0.224, 0.204, and 0.597 μM, respectively, while metabolite 3 displayed no effect. Our results suggest that the dominant Enterococcus species could modulate potential precursors of fungal origin and change their biological activity.

Background and Purpose: The unilateral onset and persistent asymmetry of motor symptoms are important characteristics of Parkinson's disease (PD). By using scales and wearable sensors, this study explored whether motor symptom laterality could affect non-motor symptom and gait performance.Methods: A total of 130 right-handed patients with PD were enrolled in our study and were divided into two groups according to the side of predominant motor symptom presentation by using the Unified Parkinson's Disease Rating Scale part III. We measured the non-motor symptoms with the Non-motor symptoms Scale, sleep quality with the Parkinson's Disease Sleep Scale and Pittsburgh sleep quality index, cognitive function with the Mini-mental State Examination and Montreal Cognitive Assessment, quality of life with the Parkinson's Disease Questionnaire-39, and the severity of anxiety and depression with the Hamilton Anxiety Scale and Hamilton Depression Scale, respectively. All participants underwent the instrumented stand and walk test, and gait data were collected using a set of JiBuEn gait analysis system.Results: We observed that left-dominant symptom PD patients (LPD) were associated with a greater impairment of sleep quality than right-dominant symptom PD patients (RPD). We found no difference between LPD and RPD in terms of gait performance. However, compared with the severe asymmetry RPD patients (RPD-S), severe asymmetry LPD patients (LPD-S) showed a shorter stride length and decreased range of motion of hip joints.Conclusions: In this study, LPD was associated with a more severe sleep-related dysfunction than RPD. In addition, LPD-S exhibited more gait impairments than RPD-S. Considering that motor symptom laterality may affect the non-motor symptom and gait performance, it should be taken into account when evaluating and treating PD patients.

Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.

Background and Purpose. Patients with early-stage Parkinson’s disease (PD) have gait impairments, and gait parameters may act as diagnostic biomarkers. We aimed to (1) comprehensively quantify gait impairments in early-stage PD and (2) evaluate the diagnostic value of gait parameters for early-stage PD. Methods. 32 patients with early-stage PD and 30 healthy control subjects (HC) were enrolled. All participants completed the instrumented stand and walk test, and gait data was collected using wearable sensors. Results. We observed increased variability of stride length (SL) (P

Objective. Rapid eye movement (REM) sleep behavior disorder (RBD) is a common symptom in Parkinson’s disease (PD), and patients with PD-RBD tend to have an increased risk of cognitive decline and have the tendency to be akinetic/rigidity predominant. At the same time, the mechanisms of RBD in patients with PD remain unclear. Therefore, this study aimed to detect the structural and functional differences in patients with PD-RBD and PD without RBD (PD-nRBD). Methods. Twenty-four polysomnography-confirmed patients with PD-RBD, 26 patients with PD-nRBD, and 26 healthy controls were enrolled. Structural and functional patterns were analyzed based on voxel-based morphometry and seed-based functional connectivity (FC). Correlations between altered gray matter volume (GMV)/FC values and cognitive scores and motor impairment scores in PD subgroups were assessed. Results. Compared with patients with PD-nRBD, patients with PD-RBD showed relatively high GMV in the cerebellar vermis IV/V and low GMV in the right superior occipital gyrus (SOG). For the FC, patients with PD-RBD displayed lower FC between the right SOG and the posterior regions (left fusiform gyrus, left calcarine sulcus, and left superior parietal gyrus) compared with the patients with PD-nRBD. The GMV values in the right SOG were negatively correlated with the Unified PD Rating Scale-III scores in patients with PD-RBD but positively correlated with delayed memory scores. The GMV values in the cerebellar vermis IV/V were positively correlated with the tonic chin EMG density scores. There were positive correlations between the FC values in the right SOG-left superior parietal gyrus and MoCA and visuospatial skills/executive function scores and in the right SOG-left calcarine sulcus and delayed memory scores. Conclusion. Higher GMV in the cerebellum may be linked with the abnormal motor behaviors during REM sleep in patients with PD-RBD, and lower GMV and FC in the posterior regions may indicate that PD-RBD correspond to more serious neurodegeneration, especially the visuospatial–executive function impairment and delayed memory impairment. These findings provided new insights to learn more about the complicated characteristics in patients with PD-RBD.

Purpose. As the most frequent and earliest type of psychotic phenomenon in Parkinson’s disease (PD), minor hallucination (MH) can occur before the onset of motor symptoms. This sensation may be an early predictor of severe psychotic and cognitive states and is often overlooked in clinics. This study was aimed at providing a comprehensive and in-depth understanding of MHs. Patients and Methods. Demographic information was obtained from 262 patients with PD, and a series of clinical assessment questionnaires were provided. According to the result of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part I, the patients were classified into the MH and nonhallucination (NH) groups. Results. MHs were the most common psychotic symptom with 38.9% prevalence. The most frequent MH was visual illusion, especially object misidentification. Three minor phenomena were somewhat consistent in terms of external factors, temporal factors, and content. Disease duration, daily levodopa equivalent dose, and percentage of levodopa and dopamine-receptor agonist use were remarkably greater in the MH group than in the NH group. After covariate control, the MH group had worse life quality and more severe nonmotor symptoms, including poor sleep quality and rapid eye movement sleep behavior disorder (RBD), than the NH group. The binary logistic regression model showed that RBD, sleep quality, and health-related life quality were associated with MHs. Conclusion. A high prevalence of MHs was observed in patients with PD. Further studies are needed to confirm and expand the identified clinical factors related to MH, which have potential prognostic and therapeutic implication.

Purpose: Parkinson's disease (PD) patients frequently present with sleep disorders. This study was designed to assess the impact of nonmotor symptoms (NMSs) on sleep quality in early-stage PD patients with and without cognitive dysfunction.Materials and Methods: A sample of 389 early-stage PD patients (modified Hoehn and Yahr score ≤ 2.5, duration ≤ 5 years) was recruited for the present study. The Non-Motor Symptoms Questionnaire (NMS-Quest) was used to screen for global NMSs. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAMD). PD motor symptoms were measured with the Unified PD Rating Scale (UPDRS), part III. The Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive status, and the PD Sleep Scale (PDSS) was used to quantify sleep quality. Polysomnography (PSG) was used for objective assessment of sleep.Results: In our sample, approximately one-quarter of the PD patients suffered from sleep disturbances (23.7%). Our results also confirmed the high prevalence of cognitive dysfunction in patients with PD (39.8%). In patients with cognitive dysfunction, higher percentage of sleep disorders (34.8 vs. 16.2%, P < 0.01) was observed. They also with lower PDSS score, sleep efficiency (SE) and longer sleep lantency (SL) and wake after sleep onset (WASO) (All P < 0.05). In total, the patients who suffered from NMSs, such as depressive symptoms, anxiety symptoms, urinary tract symptoms and hallucinations/delusions, had poorer sleep quality. Better cognition may predict better sleep quality. In patients with cognitive dysfunction, the NMS-Hallucinations/delusions score was the most important risk factor for sleep disorders. In patients without cognitive dysfunction, NMSs such as anxiety and cognition and medication were related to sleep disorder.Conclusions: NMSs in early-stage PD are highly associated with and are determinants of subjective sleep quality. Future studies should focus on elucidating the pathophysiology of these symptoms.

Background. Previous studies found levodopa could improve the activity of the ankle joints of patients with Parkinson’s disease (PD). But ankle joint movement is composed of four motion ranges. The specific changes of four motion ranges in PD remain unknown. Objective. The purpose of this study was to decompose the complex ankle joint movement, measure ankle joint changes before and after the acute levodopa challenge test (ALCT), and investigate the effects of these parameters on gait performance. Methods. 29 PD patients and 30 healthy control subjects (HC) completed the Instrumented Stand and Walk (ISAW) test and gait parameters were collected by the JiBuEn gait analysis system. The percentage of improvement of gait data and the UPDRS III in the on-drug condition (ON) were determined with respect to the off-drug condition (OFF). Results. We observed a reduction in the heel strike angle (HS), 3-plantarflexion (3-PF) angle, and 4-dorsiflexion (4-DF) angle of ankle joints. We did not find significant difference in the toe-off angle (TO), 1-plantarflexion (1-PF) angle, and 2-dorsiflexion (2-DF) angle among three groups. Stride length improvement rate was significantly correlated with HS (rs = 0.616, P

Synthesis of azido(trimethylsilyl)acetylene (6) was performed by treating the iodonium salt 5 with highly soluble hexadecyltributylphosphonium azide (QN3) at −40 °C. Although this product is very unstable, it can nevertheless be trapped by the click reaction with cyclooctyne to give the corresponding 1,2,3-triazole, and also directly characterized by 1H- and 13C-NMR data as well as IR-spectra, which were measured in solution at low temperature and in the gas phase. The thermal or photochemical decay of azide 6 leads to cyano(trimethylsilyl)carbene. This is demonstrated not only by quantum chemical calculations, but also by the trapping reactions with the help of isobutene.