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Abstract Background Thermostability is a fundamental property of proteins to maintain their biological functions. Predicting protein stability changes upon mutation is important for our understanding protein structure–function relationship, and is also of great interest in protein engineering and pharmaceutical design. Results Here we present mutDDG-SSM, a deep learning-based framework that uses the geometric representations encoded in protein structure to predict the mutation-induced protein stability changes. mutDDG-SSM consists of two parts: a graph attention network-based protein structural feature extractor that is trained with a self-supervised learning scheme using large-scale high-resolution protein structures, and an eXtreme Gradient Boosting model-based stability change predictor with an advantage of alleviating overfitting problem. The performance of mutDDG-SSM was tested on several widely-used independent datasets. Then, myoglobin and p53 were used as case studies to illustrate the effectiveness of the model in predicting protein stability changes upon mutations. Our results show that mutDDG-SSM achieved high performance in estimating the effects of mutations on protein stability. In addition, mutDDG-SSM exhibited good unbiasedness, where the prediction accuracy on the inverse mutations is as well as that on the direct mutations. Conclusion Meaningful features can be extracted from our pre-trained model to build downstream tasks and our model may serve as a valuable tool for protein engineering and drug design.

Wide-angle metalenses in the longwave infrared have shown great advantages over the traditional refractive doublets or triplets, due to light weight, CMOS compatibility, and low cost. However, previous endeavors have been plagued by challenges including a narrow waveband, large F-number, distortion, and spherical aberration. To address these problems, this study introduces two dispersive metasurfaces, placed near the front focal plane and upon the rear plane of a plano-convex lens, to correct optical aberrations. Utilizing this methodology, we propose and experimentally demonstrate an aberration-corrected hybrid metalens for thermal imaging in the 8–12 μm waveband, featuring an FOV of 24°, F-number of 1.2, and diameter of 12.2 mm. The developed hybrid metalens rigorously evaluated, exhibits Modulation Transfer Function (MTF) values exceeding 0.2 at 20 Lp/mm across the full FOV, and features an average transmission of 48.7 %, a relative focusing efficiencies of up to 42.1 %, polarization insensitivity and broadband imaging capacity. These results emphasize the potential applications of our system in diverse fields, such as camera lenses, autonomous driving, healthcare, and environmental monitoring.

Objective To investigate the effect of bone window closure on moderate to severe traumatic brain injury (TBI) in mice by controlled cortical impact (CCI). Methods A total of 200 healthy male mice were divided into 2 groups for moderate and severe TBI. Fifty were randomly selected from each group for bone window closed, and the remaining 50 were not closed. The intracranial pressure (ICP) was monitored, the water content of brain tissue and the volume of cerebral edema were measured, the degree of neurological impairment was assessed by modified Neurological Severity Score (mNSS), and the spatial learning ability and memory were evaluated by Morris water maze test. Nissl staining assessed the degree of neuronal damage in the cerebral cortex and CA1 region of the hippocampus. Results For ICP, there were differences in ICP between the bone window closed group and the unclosed group in both the moderate and severe TBI (P = 0.007, 0.000). There were also significant differences in ICP at different observation time points after modeling (P = 0.000, 0.000). The ICP on 1 d of the moderate bone window closed group was higher than that in the moderate bone window unclosed group (P = 0.009), 1 d (P = 0.000) and 3 d (P = 0.038) of the severe bone window closed group was higher than that of the severe bone window unclosed group. On 7 d, the ICP in the moderate bone window closed group (P = 0.000, 0.000) and the severe bone window closed group (P = 0.000, 0.008) was lower than that on 1 and 3 d, and the ICP on 3 d was also lower than that on 1 d (P = 0.000, 0.000). The ICP in the moderate bone window unclosed group on 7 d was lower than that on 1 d (P = 0.031). The water content of brain tissue was lower on 1 d (P = 0.028), 3 d (P = 0.023) and 7 d (P = 0.023) in severe bone window closed group than that of severe bone window unclosed group. The volume of brain edema in the bone window closed group was smaller than that in the bone window unclosed group (P = 0.021, 0.037). In the evaluation of the degree of neurological impairment, there were differences in mNSS scores at different observation time points between the bone window closed group and the bone window unclosed group (P = 0.000, 0.001). On 7 d, the mNSS scores of the moderate bone window closed group (P = 0.002), the moderate bone window unclosed group (P = 0.013) and the severe bone window closed group (P = 0.009) were all lower than those on 1 d. The mNSS scores of the severe bone window closed group (P = 0.006) and the severe bone window unclosed group (P = 0.002) were all lower than those of 3 d. Morris water maze test showed that the platform latency of mice in the severe bone window closed group was longer than that in the severe bone window unclosed group (P = 0.045), and the target quadrant residence time was shorter than that in the severe bone window unclosed group (P = 0.025). Nissl staining showed compared with the moderate bone window unclosed group, the density of Nissl bodies in cerebral cortex neurons was decreased, the staining was lighter, and the density of Nissl bodies in cerebral cortex neurons of CA1 region of hippocampus was decreased, the Nissl staining was lighter and the shape was blurred in the moderate bone window closed group. In severe TBI model mice, compared with the bone window unclosed group, the density of Nissl bodies in cerebral cortex and hippocampal CA1 region of the bone window closed group was decreased, the staining was blurred, and more metachromic particles appeared, hippocampal CA1 region body edema, the Nissl staining blurred. Conclusions In moderate TBI model mice, bone window closure increases ICP in the acute stage, but has no significant effect on the degree of cerebral edema, neurological function and cognitive function. In severe TBI model mice, bone window closure can lead to increased ICP and decreased spatial learning ability and memory, but it can reduce the degree of brain edema and improve neurological function. It is suggested that bone window closure should be selected according to the purpose of the study.

Virtual synchronous generator (VSG) enhances the stability of distributed power sources during grid connection by simulating the operating principle of a synchronous generator and introducing the virtual inertia and damping coefficient. However the traditional VSG control strategy struggles to address abrupt changes in grid voltage phase and amplitude when the voltage drops in the grid. Therefore, a low voltage ride-through control method for VSG based on phase and amplitude compensation is proposed. Firstly, the different effects of voltage drops and recovery on the power grid are analyzed. Secondly, during voltage drops, the purposes of overcurrent suppression, rapid stabilization of output power, and reactive power compensation are achieved by controlling the phase and amplitude difference between VSG output voltage and grid voltage within the allowable range. Then, during voltage recovery, rapid compensation eliminates the phase difference and amplitude difference between VSG output voltage and grid voltage to suppress overcurrent and other problems caused by grid voltage jumps. Finally, the effectiveness of the proposed control strategy is verified by MATLAB/Simulink simulation. The simulation results show that it can effectively suppress the overcurrent and realize reactive power compensation.

For seeking the cause of the increase in dough water absorption rate after cold plasma treatment, this study adopted low-pressure, radiofrequency 120 W helium cold plasma (CP) to treat wheat flours from 0 s to 180 s. Results showed that water absorption rate, conductivity, values of water and sucrose solvent retention capacity (SRC), and paste breakdown value in wheat flours increased significantly with increasing CP treatment time. To further explore the change causes in these physiochemical indexes, we developed a seven- parameter polynomial , (M was equilibrium moisture (%), ERH was equilibrium relative humidity (decimal), t was temperature (℃), and A~G were parameters. This polynomial could fit moisture sorption isotherms (20-35 ℃ and ERH 10%-90%) of helium CP treated flours, and the goodness-of-fit indexes were superior to those of modified Chung-Pfost (commonly used) and four-parameter polynomial (without temperature term) equations. The seven-parameter polynomial equation clearly showed the hysteresis loops between moisture adsorption and desorption isotherms of flour samples, which shifted downward with increasing temperature. The hysteresis degree showed a parabolic shape curve with increasing ERH, and the vertex of the parabola was at the range of 40-50% ERH. CP treatment shifted the monolayer adsorption sites to multi-molecular adsorption sites ahead of schedule, from ERH 50% to 40%. Further analysis using Dent model showed that the helium CP treatment was able to reduce the mono-layer moisture content and spreading pressure in wheat flour, and increase the elasticity of a capillary wall. The ability of water molecules was increased to form hydrogen bonds with the chemical components, which promoted the uniform distribution and permeation of water molecules into flour particles. Infrared spectral scanning showed that the degree of short-range order at the surface of starch granules and the interaction between protein and starch tended to increase with increasing CP time. Helium cold plasma technology has potential application in improving flour processing quality.

To understand the cause for the increasing water absorption rate of wheat shorts after cold plasma treatment, a dynamic moisture adsorption instrument was used to measure the moisture sorption isotherms of samples treated with 120 W low-pressure strong radio frequency helium or oxygen CP for different times. The result was that the Caurie equation can fit an isotherm, and its coefficient C0 gived the density of water adsorbed by the sample. For adsorbed or desorbed samples, as the helium or oxygen CP treatment time at the same power increased, there was no difference in the density of adsorbed water, and the coefficient M0 gived the adsorbed water content of the monomolecular layer of the sample. For adsorbed or desorbed samples, as the helium CP treatment time at the same power increased, the water content of the monomolecular layer increased significantly. For samples treated with oxygen plasma, the content of the adsorbed monomolecular layer water first decreased and then increased as the treatment time increased, while the desorbed single-molecule water content showed a decreasing trend with the increased time. In order to improve the fitting of the Caurie equation, M0 was corrected to A+Bt (t was the temperature, A and B were constants). Analysis of the coefficients of the modified Caurie equation showed that as the 120 W helium CP treatment time (0~180 s) increased, the monomolecular layer of water, the number of adsorbed water molecule layers, the bound water content, and the water adsorption surface area all showed a continuous increase trend. For oxygen CP, these indicators showed an increasing trend in the first 60 s of processing, and then showed a decreasing trend if the processing time was extended. The results showed that compared with oxygen-cold plasma, high-energy helium-cold plasma improved the hydrophilicity of wheat shorts proteins and polysaccharides. As the treatment time increased, the surface area and number of layers of water adsorbed by these macromolecules and the monomolecular layer, and the bound water content steadily continued to increase.

Abstract Respiratory syncytial virus (RSV) is one of the most important pathogens causing respiratory tract infection in humans, especially in infants and the elderly. The identification and structural resolution of the potent neutralizing epitopes on RSV fusion (F) protein enable an “epitope-focused” vaccine design. However, the display of RSV F epitope II on the surface of the widely-used human hepatitis B virus core antigen (HBcAg) has failed to induce neutralizing antibody response in mice. Here, we used the hepadnavirus core protein (HcAg) from different mammalian hosts as scaffolds to construct chimeric virus-like particles (VLPs) presenting the RSV F epitope II. Mouse immunization showed that different HcAg-based chimeric VLPs elicited significantly different neutralizing antibody responses, among which the HcAg derived from roundleaf bat (RBHcAg) is the most immunogenic. Furthermore, RBHcAg was used as the scaffold platform to present multiple RSV F epitopes, and the immunogenicity was further improved in comparison to that displaying a single epitope II. The designed RBHcAg-based multiple-epitope-presenting VLP formulated with MF59-like adjuvant elicited a potent and balanced Th1/Th2 immune response, and offered substantial protection in mice against the challenge of live RSV A2 virus. The designed chimeric VLPs may serve as the potential starting point for developing epitope-focused vaccines against RSV. Our study also demonstrated that RBHcAg is an effective VLP carrier for presenting foreign epitopes, providing a promising platform for epitope-focused vaccine design.

The low-pressure radio-frequency (RF) cold plasma equipment has been developing in China for over 20 years. This equipment can significantly shorten rice cooking time and increase the solid solubility in the porridge. The safety evaluation of cold plasma technology in food industry is being carried out during the recent five years. This study measured the moisture desorption/adsorption isotherms of milled rice treated zero to four times by 120 W-20 s helium cold plasma (CP, 140 Pa, 13.56 MHz, the distance from plasma resource to the samples is 3 cm, 300 g samples were treated each time). In the range of 5 to 45 ℃ and 10% to 90% RH, in contrast to the untreated samples, CP repeat treatments did not change the hygroscopic properties such as monolayer and multilayer moisture properties and the moisture content of safe storage, but they increased hydrophilicity and water absorption rate of milled rice with a significant decrease in water contract angle. This study gives basic data for the safe storage of CP-treated milled rice.

Abstract For a certain functional building group, the coupling relationship between the load of a single unit and entire building groups lies in the spatial and temporal patterns personnel distribution. Using the DeST (Designer's Simulation Toolkit) method, the personnel flow trajectory in a university campus in Shanghai was analyzed and the established energy consumption calculation model based on personnel flow trajectory of university buildings. It is proposed that personnel mobility should be included in the application of DeST to predict the total load of building groups. The results show that after the people flow trajectory was included, the total annual accumulated load decreased from 27.01 to 19.39 GWh, reducing by 28.20%; the hourly load fluctuation became more stable, the daily peak load decreased by 22.57%, and the daily peak valley difference decreased by 43.74%. The results suggest that the prediction for the air conditioning load of building complexes would be better when the trajectory of human flow is considered, minimizing unnecessary system scale and investments. Under the “double carbon” policy, the personnel flow trajectory model can effectively reduce waste in air conditioning energy consumption in campus buildings.

This study proposed the multi-coupling grouting system with the aim to tackle green mine problems such as surface collapse, water resources destruction and coal based solid waste accumulation.Successfully applied, this system yielded the following major achievements: this study (1) probed into the patterns of development and evolution in mining separation space and primary fracture space, and conducted the intelligent identification of grouting space by means of theoretical analysis, physical and numerical simulation and field detection.(2) prepared multi-source inorganic high-performance grouting materials for different scenarios by using coal-based solid wastes (coal gangue, fly ash), and developed a new KEP grouting material with underwater dispersion resistance, high volume coefficient and high plastic strength.(3) applied cluster well and feather well to grouting hole drilling and and developed an all-weather, high pump pressure and large flow intelligent grouting system; The reinforcement grouting technology is applied for the first time to strengthen the effect of grouting to reduce settlement.(4)put forward the technology system of grouting effect monitoring and detection, and emphatically expounded the borehole detection method of combining drilling core and well logging.(5)formed an intelligent technology system based on the methods of separation space grouting to reduce settlement and treat waste, caving zone grouting to treat waste, goaf grouting to strengthen foundation bearing capacity and treat waste, and roof fissure grouting to control water gushing as the core.Engineering demonstrations of this system have been carried out in Xiadian coal mine, Xinpu phosphate mine, Caojiatan coal mine, Gaojiabao coal mine and other places, which yielded good results.

Abstract An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

ObjectiveTo determine the epidemiological characteristics of norovirus infections in Lin’an District， Hangzhou City from 2012 to 2020， and provide scientific evidence for improving preventive and control measures.MethodsDescriptive epidemiological methods were used to characterize the epidemic and conduct statistical analysis to determine related factors.ResultsA total of 37 clustered outbreaks of norovirus infection were reported in Lin’an District of Hangzhou from 2012 to 2020， including 8 outbreaks in kindergartens， 15 ones in elementary schools， 8 ones in middle and high schools， 2 ones in universities， and 4 other ones. The total number of cases with norovirus infection was 1 194， with the average attack rate of 3.76%. The incidence of norovirus was higher in winter and spring. It was also higher in urban areas， followed by suburban and mountainous areas neighbored to traffic lines. Moreover， attack rates differed significantly by transmission routes， including mixed contact and aerosol transmission， contact transmission， food-borne transmission， and water-borne transmission （χ2=186.91，P

ObjectiveTo systematically compare the bowel cleaning ability, patient tolerance and safety of oral sodium phosphate tablets (NaPTab) and oral polyethylene glycol electrolyte lavage solution (PEGL) to inform clinical decision making.MethodsPubMed, Embase, CBM, WanFang Data, CNKI, and VIP databases were searched for studies that used randomized controlled trials (RCTs) to compare the roles of NaPTab and PEGL in bowel preparation before colonoscopy. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias in the included papers. A meta-analysis was performed using RevMan 5.3 software.ResultsA total of 13 RCTs were eligible for inclusion, including 2,773 patients (1,378 and 1,395 cases in the NaPTab and PEGL groups, respectively). Meta-analysis revealed no significant difference in the cleansing quality of the NaPTab and PEGL groups [RR 1.02, 95% CI (0.96–1.08), P = 0.46]. The incidence of nausea was lower in the NaPTab group than in the PEGL group [RR 0.67, 95% CI (0.58–0.76), p < 0.00001]. Patients rated the taste of NaPTab higher than PEGL [RR 1.33, 95% CI (1.26–1.40), P < 0.00001]. Willingness to repeat the treatment was also higher in the NaPTab group than in the PEGL group [RR 1.52, 95% CI (1.28–1.80), P < 0.00001]. Both serum potassium and serum calcium decreased in both groups after the preparation; however, meta-analysis revealed that both minerals decreased more in the NaPTab group than in the PEGL group [MD = 0.38, 95% CI (0.13–0.62), P = 0.006 for serum potassium and MD = 0.41, 95% CI (0.04–0.77), P = 0.03 for serum calcium]. Meanwhile, serum phosphorus increased in both groups after the preparation; however, levels increased more in the NaPTab group than in the PEGL group [MD 4.51, (95% CI 2.9–6.11), P < 0.00001].ConclusionsWhile NaP tablets and PEGL were shown to have a similar cleaning effect before colonoscopy, NaP tablets had improved patient tolerance. However, NaP tablets had a strong effect on serum potassium, calcium, and phosphorus levels. For patients with low potassium, low calcium, and renal insufficiency, NaP tablets should be prescribed with caution. For those at high-risk for acute phosphate nephropathy, NaP tablets should be avoided. Given the low number and quality of included studies, these conclusions will require additional verification by large high-quality studies.Systematic review registration10.37766/inplasy2023.5.0013, identifier: NPLASY202350013.

The research focuses on the conception and experience of the Basic Law of Food Education in Japan, analyzes its conception, and draws the experience of the implementation of "food education" in Japan: Focusing on giving justice and responsibility by means of law; Building a multi-subject cooperation system under the leadership of the government; Implementing an all-round "food education" promotion path and emphasizing the dynamic nature of the "food education promotion basic plan" are the practical experience of "food education" of the law. In order to give play to the educational value of "food breeding" in improving the diet of Chinese children, we can learn from the following aspects: Pay attention to the matching of "food breeding" laws; Establish and improve government management systems and mechanisms; Establish a trinity of family, school and society education model and carry out a long-term follow-up survey of children's dietary status.

The implementation of targeted therapies for breast cancer has been a challenge. Saikosaponin D (SsD), a triterpene saponin derived from Bupleurum, exhibits potential therapeutic properties for cancer therapy. Here, the role of SsD in broad antiproliferation effects in breast cancer was investigated, and the SsD pharmaceutical efficacy was evaluated by metabolomics analysis. Low (0.4 mg/kg) and high (2.0 mg/kg) concentrations of SsDs were used to treat breast cancer tumors in mice by intraperitoneal injection. Blood samples of mice were collected and the serum samples were extracted after SsD administration for different days. Subsequently, the serum samples were analyzed by ultra-high performance liquid chromatography tandem Orbitrap mass spectrometry (UPLC-Orbitrap MS). According to the “80% rule”, UPLC-Orbitrap MS data were processed and proper ions were screened out for further analysis. Statistical methods including one-way analysis of variance (One-way ANOVA), principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were performed to cross validate the reasonable and accuracy of the models. Representational metabolite ions present significant differences acquired by comparison within/between control group, SsD low concentration group and SsD high concentration group. The results of animal survival experiments demonstrated that SsD had obvious therapeutic effect on tumor. Mice treated with low and high concentrations of SsD showed 60% and 80% survival rate, respectively, with a significant increase in survival compared to untreated control mice. Metabonomic results showed that 12 target metabolite ions including pipecolic acid, N-acryloylglycine, 3-methyleneindolenine, L-kynurenine, phenylethylamine, DL-2-aminooctanoic acid, N (6)-methyllysine, indoleacetaldehyde, 3-methylhistamine, hexanoylglycine, hypoxanthine and hexanoylcarnitine were obtained by intra-group (in control group) screening. The signal intensities of these 12 ions changed significantly in the process of tumor growth, which provided theoretical basis for the study of tumor development and evolution. Meanwhile, 7 important metabolite ions including 3-methylene-indolenine, phenylethylamine, pipecolic acid, L-kynurenine, indoleacetaldehyde, 5-acetylamino-6-formylamino-3-methyluracil and proline betaine were obtained by analyzing inter-group data (compared among three groups), and the first 5 metabolite ions were overlapped with the ions in the list of intra-group screening. Moreover, the biological significances of the selected ions with significant difference were investigated, and two highly correlated manifested metabolic pathways including amino acid metabolism and nucleotide metabolism were discussed. Overall, the results derived from intra-group metabolomic analysis were highly correlated with the inter-group results, and the metabolites along the relevant pathways deserve further attention. This study provides a practical strategy for targeting metabolic analysis using natural product to improve the survival of patients with breast cancer.

Objective To explore the risk factors of pain in de novo Parkinson's disease (PD) patients. Methods A total of 129 de novo PD patients collected from The Affiliated Brain Hospital of Nanjing Medical University from October 2018 to September 2021 were included. According to the Item ⁃17 of the Unified Parkinson's Disease Rating Scale Ⅱ (UPDRSⅡ⁃17th), patients were classified as PD patients without pain (UPDRSⅡ⁃17th was 0, n = 88) and PD patients with pain (UPDRSⅡ⁃17th ≥ 2, n = 41）. Mini⁃ Mental State Examination (MMSE) and corrected Montreal Cognitive Assessment (corrected MoCA) were used to assess cognitive function. Meanwhile, Hamilton Depression Rating Scale ⁃24 Items (HAMD ⁃24) was used to assess the depression status and the UPDRSⅢ was used to assess the motor function. The modified version of Hoehn ⁃Yahr staging was used to assess disease severity. The related risk factors of pain in PD patients were analyzed by univariate and multivariate forward Logistic regression. Results The in of pain in PD patients was 31.78% (41/129). Compared with PD without pain group, PD with pain group had lower scores in MMSE (Z = ﹣2.389, P = 0.017) and corrected MoCA (Z = ﹣2.166, P = 0.030), but higher scores in HAMD-24 (Z = ﹣4.024, P = 0.000), UPDRS Ⅲ (Z = ﹣3.639, P = 0.000）and Hoehn-Yahr staging grading (Z = ﹣2.232, P = 0.026). Further analysis of the differences between 2 groups in 7 domains of HAMD-24 showed PD with pain group had higher scores of the anxiety/somatization (Z = ﹣3.707, P = 0.000), mental disorder (Z = ﹣2.519, P = 0.012), retardation symptom (Z = ﹣2.048, P = 0.041), sleep disturbances (Z = ﹣3.484, P = 0.000) and despair symptom (Z = ﹣3.069, P = 0.002) than PD without pain group. Logistic regression analysis showed long duration (OR = 1.354, 95%CI: 1.013-1.809; P = 0.041), high HAMD-24 score (OR = 1.095, 95%CI: 1.033-1.162; P = 0.002) and high UPDRS Ⅲ score (OR = 1.040, 95%CI: 1.001- 1.082; P = 0.046) were risk factors of pain in PD patients. Conclusions Pain in PD has a high incidence in de novo PD patients. Long duration, a depressed state and severe motor symptoms are main risk factors for the development of pain in PD patients.

Objective To analyze the detection rates of mental disorders in women with subjective depressive symptoms during pregnancy and the postnatal period. Methods From March 1st 2020 to February 28th 2021, Patient Health Questionnaire-9 items (PHQ-9) and Edinburgh Postnatal Depression Scale (EPDS) were used to screen pregnant women and mothers who were established in a third-grade hospital. The women with PHQ-9≥5 or EPDS≥9 were followed up. Mini-International Neuropsychiatric Interview (MINI) was used to confirm the detection rates of mental disorders. Results Of the 342 women who were followed up, 24 (7.0%) were diagnosed with depressive episodes. There were 17 cases had depression in the past. Among them 3 women had a history of depression before pregnancy, and 14 had the first episode after pregnancy. The detection rate of depression in the second trimester is higher than that in the first and third trimester; 9 (2.6%)with (hypo)manic episodes; 6 (1.8%) with panic disorder; 13(3.8%) with agoraphobia; 3(0.9%) with social phobia; 15(4.4%) with generalized anxiety disorder; 6 (1.8%)with obsessive-compulsive disorder. Eighteen women suffered from two or more mental disorders, accounting for 29.0% of the total number of diagnosed mental disorders. Conclusions A variety of mental disorders occur in women with subjective depressive symptoms during pregnancy and the postnatal period, and comorbidity is a common finding. Pregnant women with depression may have several episodes during this period. So it is necessary to evaluate their mental status professionally.

Abstract The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

The dynamic response of geosynthetic reinforced embankment under traffic moving load has attracted increasing attentions in the engineering field. A 3D model of geosynthetic reinforced embankment was established by using the ABAQUS finite element software in this paper, which was used to analyze the dynamic stress and deformation of geosynthetic reinforced embankment under moving load. The traffic load was simulated by two moving rectangular plane loads. Fortran subroutine was developed to control the amplitude, range, and speed of the moving load. The equivalent linear viscoelastic model was developed to simulate embankment fill to reflect the viscoelasticity of embankment fill. The geogrid was simulated by T3D2 truss element. The infinite element was used to reduce the boundary effect caused by model size. The numerical model of geosynthetic reinforced embankment under moving load was established without considering drainage consolidation. Based on the results of the existing literature and the results of this paper, the cross-section deformations of the geosynthetic reinforced embankment and the stress at the embankment top surface were compared and verified. The dynamic stress distribution in the longitudinal section and transverse section and the vertical dynamic stress distribution characteristics of the geosynthetic reinforced embankment under moving load were also analyzed. The results showed that the dynamic stress and deformation decayed rapidly within the range of 1.0 m on the embankment top surface and gradually transitioned to an equivalent uniform load with small amplitude. At the same depth, the attenuation coefficient of dynamic stress under the wheel load was the smallest, followed by that at the center of double wheel loads, and the attenuation coefficient at the outer edge of the wheel load was the largest.

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.

Objective: This article is aimed to explore the influence of closed/open conditions on the flavor compounds of Maillard reaction. Methods: The species and amounts of flavor compounds produced from Tyrosine-based Maillard reactions under closed/open conditions in different solvents and reaction temperatures were determined by GC-MS. Results: The results showed that the species and contents of flavor products are quite different under closed and open conditions. The amounts of alcohol flavor compounds were higher in closed system, while the amount of esters and ketones were higher inopensystem. Conclusion: The amounts of active oxygen and intermediates produced during the reactions likely result in the difference between closed and opensystems from the proposed mechanisms.

Due to the complexity of road in open-pit mine, the existing truck travel time prediction methods are difficult in the actual deployment. This leads to the truck optimal scheduling system only realizing scheduling instead of optimization. A combined prediction model of truck multi-section travel time in open pit mine based on velocity field is proposed. The open-pit mine road is divided into multiple road sections. the random forest algorithm is used to construct the unit prediction model to predict the travel time of the truck in each section. Then the predicted values of the unit prediction models are accumulated to obtain the travel time predicted value of the truck on in the composite road section. In order to improve the prediction precision, the average velocity of the truck is taken as an influence factor of the travel time. The velocity field is constructed according to the collected velocity information of the truck. The average value of the truck velocity at all points on a road section is calculated, which is approximate to the average velocity of the truck on the road section, and the average velocity is input into the unit prediction model. Based on the data of truck schedule information in truck dispatching system of Yimin Open-pit Mine, the combined prediction model is trained, and the prediction precision and real-time performance of the model are tested. The results show that the combined prediction model of truck travel time in multiple sections of open-pit mine based on velocity field has high prediction precision for truck travel time in composite road sections. The average absolute error percentage is 4.81%, which is more than 2% lower than the single prediction model based on random forest algorithm. The operation time of the combined prediction model is less than 1 s, which can realize the real-time prediction of truck travel time.

The effects of the evolution behavior of carbide on impact toughness of 1Cr-0.5Mo steel during cyclic heat treatment were investigated by quantitative metallographic method and electrolytic extraction method with SEM,XRD,EPMA and low temperature impact test. The results show that with the increasing number of cyclic heat treatment, the lamellar carbides in the pearlite structure dissolve and spheroidize gradually, and the type of carbide also changes: M3C→M23C6. Increasing the number of cyclic heat treatments promotes the precipitation and connection of M23C6 along the grain boundaries, significantly deteriorates the impact toughness of 1Cr-0.5Mo steel.When the number of cyclic heat treatments reaches 4,the M23C6 grows to chain-like at the grain boundary and the impact toughness of 1Cr-0.5Mo steel can no longer meet the requirements. During the cyclic heat treatment, the average equivalent circle diameter of the overall carbide in 1Cr-0.5Mo steel shows a trend of decrease first and then increase because of the dissolution of lamellar carbides and the Ostwald ripening of carbides.

Advanced stage primary hepatocellular carcinoma (HCC) accounts for more than half of all cases worldwide. Poor prognosis is mainly attributed to intrahepatic tumor burden caused by high-risk factors, including Vp4-portal vein tumor thrombosis or tumor occupancy of >50% of the liver. In 2020, the combination of a VEGF/PD-L1 blocker was superior to a single tyrosine kinase inhibitor and associated with a median overall survival of 19.2 months. However, overall survival dramatically declined from 19.2 months to 7.6 months for patients with high-risk factors. In this present study, the FOHAIC-1 trial, interventional hepatic arterial infusion chemotherapy of FOLFOX (HAIC-FO) showed favorable survival outcomes in patients with high-risk advanced HCC. Compared with a tyrosine kinase inhibitor, in the high-risk subgroup, HAIC-FO achieved an overall survival of 10.8 months (vs. 5.7 months, hazard ratio 0.343, 95% confidence interval, 0.219–0.538). This study also observed disease downstaging in 16 (16/130) patients who received HAIC-FO; 15 (93.8%) patients received curative or regional treatments afterward. Therefore, for advanced HCC with localized high-risk factors, the clinical efficacy of HAIC-FO is significant and may be a better option than systemic therapies.