Through comparative study, case and data analysis, this article summarizes the key points of the fourth amendment of Chinese Patent Law, and analyses the expected practical significance. Meanwhile, this article also discusses the shortcomings of the new patent law after the fourth amendment, and puts forward some suggestions for further improvement and refinement. The purpose of the fourth amendment of Chinese Patent Law is mainly to make the Chinese patent system more in line with the current technological and economic development in China as well as international cooperative innovation. The core points of the fourth amendment include: (1) strengthening patent enforcement by adopting punitive damages to intentional patent infringement, and increasing the patent protection duration extension for new pharmaceuticals, etc. (2) Promoting patent implementation by adding ‘Open Licence’ rules and improving employees’ invention regulations; (3) Improving design patent protection by expending protection duration and adopting protection for partial designs. (4) Increasing the provisions about the grace period for patent filings of inventions related to public interests. The new Patent Law 2020 will gradually show its significant practical effects. At the same time, however, there are still some regulations that need to be further clarified and refined for ensuring better implementation of the new law.

Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9–80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0–34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.

Human immunodeficiency virus (HIV) has been widely prevalent among older men (aged ≥50 years old) in Sichuan Province. The study aimed to discover associated factors with the new HIV infection in older men, and provide a scientific basis for the prevention and control of acquired immunodeficiency syndrome (AIDS) in this group. A cross-sectional survey study of newly reported HIV/AIDS and general male residents aged 50 years and older was conducted between April and June 2019, with a resample of respondents to identify cases and controls, followed by a case–control study. Logistic regression was applied to analyse the association between the selected factors and new HIV infection among older men. At last, 242 cases and 968 controls were included. The results of multiple logistic regression suggested that many factors including living alone/concentrated (OR 1.56, 95% CI 1.20–2.04, P = 0.001), have a history of migrant worker (OR 2.10, 95% CI 1.61–2.73, P < 0.001), have commercial sexual behaviour (OR 1.71, 95% CI 1.32–2.22, P < 0.001), married (OR 0.48, 95% CI 0.37–0.64, P < 0.001), have a history of HIV antibody testing (OR 0.73, 95% CI 0.56–0.96, P = 0.026), HIV-related knowledge (OR 0.55, 95% CI 0.42–0.72, P < 0.001) were associated with new HIV infection among older men. The present study revealed some potential risky/protective factors altogether. The results highlighted the direction of HIV/AIDS prevention and control among older men, and it is a social issue that requires the joint participation of the whole society.

This study aimed to investigate the characteristics of uncertainty in illness and the coping styles of patients with severe coronavirus 2019 (COVID-19) and to explore their relationship to provide effective guidance for clinical nursing. A cross-sectional survey was used to investigate 56 severe patients with COVID-19 in a designated hospital in Wuhan. A general information questionnaire, the Mishel Uncertainty in Illness Scale for Adults (MUIS-A) and the Medical Coping Modes Questionnaire (MCMQ) were used to collect the data. A statistical analysis was performed. The total score of the MUIS-A was a 66.29 ± 17.25 which was at a low level, while the total score of the MCMQ was 54.16 ± 6.39. The scores of facing and avoiding were significantly higher than those in the norm. The difference in the yielding dimension of patients with different family economic situations was statistically significant. The total score of MUIS-A correlated negatively with the coping style of facing and avoiding and positively correlated with the coping style of yielding. The coping style of patients was one of the factors influencing uncertainty in illness. Nursing staff need to pay close attention to the psychological state of their patients, understand their coping styles and actively correct negative coping styles to reduce the uncertainty in illness and promote physical as well as mental recovery.

The relationship between exposure to famine in early life and the risk of ascending aorta dilatation (AAD) in adulthood is still unclear; therefore, we aimed to examine the association in the Chinese population. We investigated the data of 2598 adults who were born between 1952 and 1964 in Guangdong, China. All enrolled subjects were categorised into five groups: not exposed to famine, exposed during fetal period, and exposed during early, mid or late childhood. AAD was assessed by cardiac ultrasound. Multivariate logistic regression and interaction tests were performed to estimate the OR and CI on the association between famine exposure and AAD. There were 2598 (943 male, mean age 58·3 ± 3·68 years) participants were enrolled, and 270 (10·4 %) subjects with AAD. We found that famine exposure (OR = 2·266, 95 % CI 1·477, 3·477, P = 0·013) was associated with elevated AAD after adjusting for multiple confounders. In addition, compared with the non-exposed group, the adjusted OR for famine exposure during fetal period, early, mid or late childhood were 1·374 (95 % CI 0·794, 2·364, P = 0·251), 1·976 (95 % CI 1·243, 3·181, P = 0·004), 1·929 (95 % CI 1·237, 3·058, P = 0·004) and 2·227 (95 % CI 1·433, 3·524, P < 0·001), respectively. Subgroup analysis showed that the effect of famine exposure on the association with AAD was more pronounced in female, current smokers, people with BMI ≥ 24 kg/m2 and hypertensive patients. We observed that exposure to famine during early life was linked to AAD in adulthood.

Salicylic acid (SA), a phytohormone, has been considered to be a key regulator mediating plant defence against pathogens. It is still vague how SA activates plant defence against herbivores such as chewing and sucking pests. Here, we used an aphid-susceptible wheat variety to investigate Sitobion avenae response to SA-induced wheat plants, and the effects of exogenous SA on some defence enzymes and phenolics in the plant immune system. In SA-treated wheat seedlings, intrinsic rate of natural increase (rm), fecundity and apterous rate of S. avenae were 0.25, 31.4 nymphs/female and 64.4%, respectively, and significantly lower than that in the controls (P < 0.05). Moreover, the increased activities of phenylalanine-ammonia-lyase, polyphenol oxidase (PPO) and peroxidase in the SA-induced seedlings obviously depended on the sampling time, whereas activities of catalase and 4-coumarate:CoA ligase were suppressed significantly at 24, 48 and 72 h in comparison with the control. Dynamic levels of p-coumaric acid at 96 h, caffeic acid at 24 and 72 h and chlorogenic acid at 24, 48 and 96 h in wheat plants were significantly upregulated by exogenous SA application. Nevertheless, only caffeic acid content was positively correlated with PPO activity in SA-treated wheat seedlings (P = 0.031). These findings indicate that exogenous SA significantly enhanced the defence of aphid-susceptible wheat variety against aphids by regulating the plant immune system, and may prove a potential application of SA in aphid control.

In this article, the electron trapping and acceleration in the wake field driven by an ultrarelativistic hollow electron beam is studied. When the hollow driver injects into plasma, there is a doughnut-shaped electron bubble formed because of the existence of a special ‘backflow’ beam in the centre of the electron bubble. At the same time, there is a transverse convergence of the hollow driver, which leads to the weakening of the backflow beam. This results in a local electron density transition at the rear of the bubble. During this process, there is an expansion of the longitudinal electron bubble size, and a bunch of background electrons is trapped by the wake field at the rear of the bubble. The tracks for the trapped electrons show that there are two sources: one is from the bubble sheath and the other is from the unique backflow beam. In the particle-in-cell simulation where the driving beam has initial energy of $1.0$ GeV per particle, the trapped beam can be accelerated to energy of more than $1.5$ GeV per particle and the corresponding transformer ratio is $1.5$. With the increase of driving beam energy up to $40.0$ GeV, a transformer ratio of $1.4$ still can be achieved. By adjusting the hollow beam density, it is possible to control the trapped beam charge value and beam quality, such as its energy spread and transverse emittance.

In the current research, a 60-d experiment was conducted with the purpose of exploring the impacts of methionine (Met) on growth performance, muscle nutritive deposition, muscle fibre growth and type I collagen synthesis as well as the related signalling pathway. Six diets (iso-nitrogenous) differing in Met concentrations (2·54, 4·85, 7·43, 10·12, 12·40 and 15·11 g/kg diets) were fed to 540 grass carp (178·47 (SD 0·36) g). Results showed (P < 0·05) that compared with Met deficiency, optimal level of dietary Met (1) increased feed intake, feed efficiency, specific growth rate and percentage weight gain (PWG); (2) increased fish muscle protein, lipid and free amino acid contents and improved fish muscle fatty acid profile as well as increased protein content in part associated with the target of rapamycin complex 1 (TORC1)/S6K1 signalling pathway; (3) increased the frequency distribution of muscle fibre with >50 µm of diameter; (4) increased type I collagen synthesis partly related to the transforming growth factor-β1/Smads and CK2/TORC1 signalling pathways. In conclusion, dietary Met improved muscle growth, which might be due to the regulation of muscle nutritive deposition, muscle fibre growth and type I collagen synthesis-related signal molecules. Finally, according to PWG and muscle collagen content, the Met requirements for on-growing grass carp (178–626 g) were estimated to be 9·56 g/kg diet (33·26 g/kg protein of diet) and 9·28 g/kg diet (32·29 g/kg of dietary protein), respectively.

The present study investigated the effects of condensed tannins (CT) on intestinal immune function in on-growing grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp were fed six diets containing different levels of CT (0, 10·00, 20·00, 30·00, 40·00 and 50·00 g/kg diet) for 70 d and then challenged with Aeromonas hydrophila for 14 d. The results showed that, compared with the control group, dietary CT (1) induced intestinal histopathological lesions and aggravated enteritis; (2) decreased lysozyme and acid phosphatase activities, complement 3 (C3), C4 and IgM contents and down-regulated the Hepcidin, liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, Mucin2 and β-defensin-1 mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) (P < 0·05); (3) down-regulated the mRNA levels of anti-inflammatory cytokines transforming growth factor (TGF)-β1, TGF-β2 (not in MI and DI), IL-4/13A (not IL-4/13B), IL-10 and IL-11 partly correlated with target of rapamycin (TOR) signalling; and (4) up-regulated the mRNA levels of pro-inflammatory cytokines interferon-γ2, IL-1β, IL-6, IL-8 (not in PI), IL-12p35, IL-12p40, IL-15 and IL-17D partly related to NF-κB signalling in the intestine of on-growing grass carp. Overall, the results indicated that CT could impair the intestinal immune function, and its potential regulation mechanisms were partly associated with the TOR and NF-κB signalling pathways. Finally, based on the percentage weight gain and enteritis morbidity, the maximum allowable levels of CT for on-growing grass carp (232·22–890·11 g) were estimated to be 18·6 and 17·4 g/kg diet, respectively.

Molluscan shells showing phenotypic variations are ideal models for studying evolution and plasticity. In north-eastern Asia, genetic and morphological diversity of the gastropod, Monodonta labio, were assumed to be influenced by both palaeoclimatic changes and current ecological factors. In this study, we examined spatial variations in shell shape of M. labio using general measurement and geometric morphometric analysis. We also investigated whether shell shape variation is best explained by environmental gradients or by genetic structuring, based on our prior molecular phylogeographic study. Two common morphological forms were observed among Chinese populations and in the adjacent Asian areas. Both the analyses revealed separation patterns in morphological variations of shell shape among the clades and populations. Environmental modelling analysis showed a significant correlation between shape variations and local maximum temperatures of the warmest month, indicating the role of natural selection in the evolution of this species. Data obtained in this study, combined with the cytochrome oxidase subunit I (COI) molecular phylogenetic data from the prior study, showed that morphological variations in M. labio were constrained by both local adaptation and phenotypic plasticity. We hypothesized that geographic separation by the Dongshan Landbridge was the first step towards its diversification, and that the temperature gradient between the East China Sea and South China Sea probably was the selective force driving the divergence of its morphological variations.

Paediatric Mycoplasma pneumoniae pneumonia (MPP) is a major cause of community-acquired pneumonia in China. Data on epidemiology of paediatric MPP from China are little known. This study retrospectively collected data from June 2006 to June 2016 in Beijing Children's Hospital, Capital Medical University of North China and aims to explore the epidemiological features of paediatric MPP and severe MPP (SMPP) in North China during the past 10 years. A total of 27 498 paediatric patients with pneumonia were enrolled. Among them, 37.5% of paediatric patients had MPP. In this area, an epidemic took place every 2–3 years at the peak, and the positive rate of MPP increased during these peak years over time. The peak age of MPP was between the ages of 6 and 10 years, accounting for 75.2%, significantly more compared with other age groups (χ2 = 1384.1, P < 0.0001). The epidemics peaked in September, October and November (χ2 = 904.9, P < 0.0001). Additionally, 13.0% of MPP paediatric patients were SMPP, but over time, the rate of SMPP increased, reaching 42.6% in 2016. The mean age of paediatric patients with SMPP (6.7 ± 3.0 years old) was younger than that of patients with non-SMPP (7.4 ± 3.2 years old) (t = 3.60, P = 0.0001). The prevalence of MPP and SMPP is common in China, especially in children from 6 to 10 years old. Paediatric patients with SMPP tend to be younger than those with non-SMPP. MPP outbreaks occur every 2–3 years in North China. September, October and November are the peak months, unlike in South China. Understanding the epidemiological characteristics of paediatric MPP can contribute to timely treatment and diagnosis, and may improve the prognosis of children with SMPP.

The associations between Chinese adolescents’ family (maternal, paternal, and sibling) relationship qualities and their adjustment were examined among 540 Chinese families over a one-year period. Path analysis revealed that father-offspring positivity was associated with lower levels of internalising problems, whereas mother-offspring conflict predicted youths’ depressive symptoms and loneliness. Controlling for parent-offspring relationships, sibling intimacy inversely predicted youths’ internalising and externalising problems, whereas sibling conflict predicted youths’ loneliness. Multigroup comparisons revealed that youth gender moderated the associations between maternal conflict and youths’ depressive symptoms, as well as sibling intimacy and youths’ loneliness. Overall, results highlight the importance of family systems for Chinese youths’ mental health and the need to study sibling relationships in future studies of Chinese families.

This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99–21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and β-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling. Finally, on the basis of the specific growth rate, against the enteritis morbidity and IgM contents, the optimum threonine requirements were estimated to be 14·53 g threonine/kg diet (4·48 g threonine/100 g protein), 15.05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively.

The present study investigated the effects of dietary vitamin A on immune function in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). Fish were fed graded levels of dietary vitamin A for 10 weeks, and then a challenge test using an injection of Aeromonas hydrophila was conducted for 14 d. The results showed that, compared with the optimum vitamin A level, vitamin A deficiency significantly decreased fish growth performance, increased enteritis morbidity, decreased intestinal innate humoral immune response and aggravated intestinal inflammation. However, liver-expressed antimicrobial peptide 2A/B mRNA in the DI and IL-6, IL-17D, IL-10, transforming growth factor (TGF)-β1 and TGF-β2 mRNA in the PI were not affected by vitamin A levels. Meanwhile, vitamin A deficiency disturbed inflammatory cytokines in the PI, MI and DI, which might be partly linked to p38 mitogen-activated protein kinase (p38MAPK) signalling and NF-κB canonical signalling pathway (IκB kinase β (IKKβ), IKKγ, inhibitor of κBα, NF-κB p65 and c-Rel) rather than NF-κB non-canonical signalling pathway (NF-κB p52 and IKKα). However, the signalling molecules NF-κB p65 and p38MAPK did not participate in regulating cytokines in the PI. These results suggested that vitamin A deficiency decreased fish growth and impaired intestinal immune function, and that different immune responses in the PI, MI and DI were mediated partly by NF-κB canonical signalling and p38MAPK signalling pathways. On the basis of percentage of weight gain, to protect fish against enteritis morbidity and acid phosphatase activity, the optimum dietary vitamin A levels were estimated to be 0·664, 0·707 and 0·722 mg /kg, respectively.

Crack propagation behaviors in a precracked single crystal Ag under mode I loading at different temperatures are studied by molecular dynamics simulation. The simulation results show that the crack propagation behaviors are sensitive to external temperature. At 0 K, the crack propagates in a brittle manner. Crack tip blunting and void generation are first observed followed by void growth and linkage with the main crack, which lead to the propagation of the main crack and brittle failure immediately without any microstructure evolution. As the temperature gets higher, more void nucleations and dislocation emissions occur in the crack propagation process. The deformation of the single crystal Ag can be considered as plastic deformation due to dislocation emissions. The crack propagation dynamics characterizing the microstructure evolution of atoms around the crack tip is also shown. Finally, it is shown that the stress of the single crystal Ag changes with the crack length synchronously.

This study investigated the effects of glycinin on the growth, intestinal oxidative status, tight junction components, cytokines and apoptosis signalling factors of fish. The results showed that an 80 g/kg diet of glycinin exposure for 42 d caused poor growth performance and depressed intestinal growth and function of juvenile Jian carp (Cyprinus carpio var. Jian). Meanwhile, dietary glycinin exposure induced increases in lipid peroxidation and protein oxidation; it caused reductions in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities; and it increased MnSOD, CuZnSOD, GPx1b and GPx4a mRNA levels, suggesting an adaptive mechanism against stress in the intestines of fish. However, dietary glycinin exposure decreased both the activity and mRNA levels of nine isoforms of glutathione-S-transferase (GST) (α, μ, π, ρ, θ, κ, mGST1, mGST2 and mGST3), indicating toxicity to this enzyme activity and corresponding isoform gene expressions. In addition, glycinin exposure caused partial disruption of intestinal cell–cell tight junction components, disturbances of cytokines and induced apoptosis signalling in the distal intestines>mid intestines>proximal intestines of fish. Glycinin exposure also disturbed the mRNA levels of intestinal-related signalling factors Nrf2, Keap1a, Keap1b, eleven isoforms of protein kinase C and target of rapamycin/4E-BP. Interestingly, glutamine was observed to partially block those negative influences. In conclusion, this study indicates that dietary glycinin exposure causes intestinal oxidative damage and disruption of intestinal physical barriers and functions and reduces fish growth, but glutamine can reverse those negative effects in fish. This study provides some information on the mechanism of glycinin-induced negative effects.