Research progress in the off-target effects of Bacille Calmette-Guérin vaccine

Bacille Calmette-Guérin(BCG)vaccine is designed to provide protection against tuberculosis(TB).However,numerous epidemiological,clinical,and immunological studies have shown that BCG vaccination affects neonatal and infant mortality,which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine.We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases,as well as the potential mechanism and influencing factors.Literature was retrieved mainly from PubMed using medical subject headings"BCG,variations,and non-specific,heterologous or off-target".Studies have showed that BCG vaccination can prevent various heterologous infections,including respiratory tract infections,leprosy,and malaria,treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy,and improve the immune responses as vaccine adjuvant.Besides,BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer,and may provide protection against autoimmune diseases.These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity,which were found to be sex-differentiated and affected by the BCG vaccine strains,sequence or time of vaccination.

A survey on the off-target effects of insecticidal double-stranded RNA targeting the Hvβ'COPI gene in the crop pest Henosepilachna vigintioctopunctata through RNA-seq

The specificity of the double-stranded RNA(dsRNA) used in the RNA interference(RNAi) technique is crucial for the success of sequence-specific gene silencing. Currently, RNAi-mediated insect control is a trending research topic.However, the off-target effects of the dsRNA in RNAi are a major concern. In this study, the ds Hvβ’COPI(coat protein complex I, β’ subunit)-treated and untreated transcriptomes of the 28-spotted potato lady beetle(Henosepilachna vigintioctopunctata) were compared to understand its off-target gene silencing effects. The RNA-seq results revealed that 63 and 44 differentially expressed genes(DEGs) were upregulated and downregulated, respectively, in the ds Hvβ’COPI treated group as compared with the control. Validation of the differential expressions of some selected DEGs via reverse transcription-quantitative PCR(RT-qPCR) analysis confirmed the reliability of the transcriptome analysis results. Further downstream analysis revealed that there were no genes homologous with Hvβ’COPI in H. vigintioctopunctata. Additionally,no genes with a >11 bp continuous match with ds Hvβ’COPI were found in the H. vigintioctopunctata transcriptome. Six genes(Hvcitron, Hvhelicase, Hvtransposase, Hvserine, Hvdynein, and Hv E3 ubiquitin) were selected to examine the offtarget activity of ds Hvβ’COPI based on their potential involvement in various H. vigintioctopunctata metabolic pathways.The severity of silencing these six off-target genes was evaluated by employing RNAi. The RNAi results confirmed the downregulation of the expression of all six genes, although there was no significant lethality. The findings of this study will be helpful in the risk analysis of future RNAi-mediated pest control experiments.

Using transcriptome Shannon entropy to evaluate the off-target effects and safety of insecticidal siRNAs

A recent breakthrough in agricultural biotechnology is the introduction of RNAi-mediated strategies in pest control.However, the off-target effects of RNAi pest control are still not fully understood. Here, we studied the off-target effects of two insecticidal siRNAs in both target and non-target insects. The results revealed that off-target effects of insecticidal siRNAs occur widely in both target and non-target insects. We classified the expression-changed genes according to their homology to the siRNA-targeted gene, related KEGG pathways with the siRNA-targeted gene and continuous matches with siRNAs. Surprisingly, the unintended significant changes in gene expression levels did not strictly match with the number of contiguous nucleotides in the siRNAs. As expected, the expression of small portions of the homologous and KEGG-related genes were significantly changed. We calculated the Shannon entropy of the transcriptome profile of the insects after injecting them with insecticidal siRNAs. Though hundreds of genes were affected in their expression levels post siRNAtreatment, the Shannon entropy of the transcriptome remained unchanged, suggesting that the transcriptome expression was balanced. Our results provide evidence that siRNAs cross-reacted with individual genes in non-target species, but did not have significant effects on the integrity of the transcriptome profiles in either target or non-target species on a genomic scale. The metric we proposed can be used to estimate the off-target effects of insecticidal siRNAs, which might be useful for evaluating the safety of RNAi in pest control.

Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Carbon Emission Effects Driven by Evolution of Chinese Dietary Structure from 1987 to 2020

Exploring carbon emission effects based on the evolution of residents’ dietary structure to achieve the carbon neutrality goal and mitigate climate change is an important task.This study took China as the research object(data excluding Hong Kong,Macao and Taiwan) and used the carbon emission coefficient method to quantitatively measure the food carbon emissions from 1987–2020,then analyzed the carbon emission effects under the evolution of dietary structure.The results showed that during the study period,the Chinese dietary structure gradually changed to a high-carbon consumption pattern.The dietary structure of urban residents developed to a balanced one,while that of rural residents developed to a high-quality one.During the study period,the per capita food carbon emissions and total food consumption of Chinese showed an increasing trend.The per capita food carbon emissions of residents in urban and rural showed an overall upward trend.The total food carbon emissions in urban increased significantly,while that in rural increased first and then decreased.The influence of beef and mutton on carbon emissions is the highest in dietary structure.Compared with the balanced dietary pattern,the food carbon emissions of Chinese residents had not yet reached the peak,but were evolving to a high-carbon consumption pattern.

Simulation of the Ecosystem Productivity Responses to Aerosol Diffuse Radiation Fertilization Effects over the Pan-Arctic during 2001–19

The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.

Effects of urbanization and forest type on species composition and diversity,forest characteristics,biomass carbon sink,and their associations in Changchun,Northeast China:implications for urban carbon stock improvement

Differences in forest attributes and carbon sequestration of each organ and layer between broadleaved and conifer forests of central and outer urban areas are not well-defined,hindering the precise management of urban forests and improvement of function.To clarify the effect of two forest types with different urbanization intensities,we determined differences in vegetation composition and diversity,structural traits,and carbon stocks of 152 plots(20 m×20 m)in urban park forests in Changchun,which had the largest green quantity and carbon density effectiveness.We found that 1.1-fold thicker and healthier trees,and 1.6-to 2.0-fold higher,healthier,denser,and more various shrubs but with sparser trees and herbs occurred in the central urban forests(p<0.05)than in the outer forests.The conifer forests exhibited 30–70%obviously higher tree aboveground carbon sequestration(including stem and leaf)and 20%bigger trees,especially in the outer forests(p<0.05).In contrast,1.1-to 1.5-fold higher branch stocks,healthier and more diverse trees were found in broadleaved forests of both the inner and outer forests(p<0.05).Plant size and dominant species had similarly important roles in carbon stock improvement,especially big-sized woody plants and Pinus tabuliformis.In addition,a higher number of deciduous or needle species positively affected the broadleaved forest of the central urban area and conifer forest of the outer urban area,respectively.These findings can be used to guide precise management and accelerate the improvement of urban carbon function in Northeast China in the future.

Health Effects of Extreme Low Temperatures and Cold Waves on Respiratory Diseases

Climate change is the most significant threat to public health and exerts myriad influences on health,including the occurrence of extreme temperature events.Studies have demonstrated that populations will experience significantly severe cold waves in the future^([1]),increasing the risk of respiratory diseases.

Tilted Perpendicular Anisotropy-Induced Spin-Orbit Ratchet Effects

Using micromagnetic simulations, we demonstrate the tilted perpendicular anisotropy-induced spin-orbit ratchet effect. In spin-orbit torque(SOT)-induced magnetization switching, the critical currents required to switch between the two magnetization states(upward and downward magnetization) are asymmetric. In addition, in the nanowire structure, tilted anisotropy induces formation of tilted domain walls(DWs). The tilted DWs exhibit a ratchet behavior during motion. The ratchet effect during switching and DW motions can be tuned by changing the current direction with respect to the tilting direction of anisotropy. The ratchet motion of the DWs can be used to mimic the leaky-integrate-fire function of a biological neuron, especially the asymmetric property of the “potential” and “reset” processes. Our results provide a full understanding of the influence of tilted perpendicular anisotropy on SOT-induced magnetization switching and DW motion, and are beneficial for designs of further SOT-based devices.

Effects of Collocational Congruency,Frequency and L2 Proficiency on the Processing of English Adjective-Noun Collocations

The present study investigates the effects of congruency and frequency on adjective-noun collocational processing for Chinese learners of English at two proficiency levels based on the data obtained in an online acceptability judgment task.The subject pool of this research included 60 English majors studying at a university in China;30 were selected as a higher-proficiency group and 30 as a lower-proficiency group according to their Vocabulary Levels Test(Schmitt et al.,2001)scores and their self-reported proficiency in English.The experimental materials were programmed to E-prime 2.0 and included six types of collocations:(1)15 high-frequency congruent collocations,(2)15 low-frequency congruent collocations,(3)15 high-frequency incongruent collocations,(4)15 low-frequency incongruent collocations,(5)15 Chinese-only items,and(6)75 unrelated items for baseline data.The collected response times(RTs)and accuracy rates data were statistically analyzed by the use of an ANOVA test and pairwise comparisons through SPSS 16.0 software.The results revealed that:(1)the adjective-noun collocational processing of Chinese English learners is influenced by collocational frequency,congruency and L2 proficiency;(2)the processing time is affected by the interaction of congruency and frequency;and(3)the interactive effect of L2 proficiency in conjunction with congruency and frequency also influences the processing quality.

Cation effects in electrocatalytic reduction reactions:Recent advances

Electrocatalytic reduction reactions,powered by clean energy sources such as solar energy and wind,offer a sustainable method for converting inexpensive feedstocks(e.g.,CO_(2),N_(2)/NO_(x),organics,and O_(2))into high-value-added chemicals or fuels.The design and modification of electrocatalysts have been widely implemented to improve their performance in these reactions.However,bottle-necks are encountered,making it challenging to further improve performance through catalyst development alone.Recently,cations in the electrolyte have emerged as critical factors for tuning both the activity and product selectivity of reduction reactions.This review summarizes recent advances in understanding the role of cation effects in electrocatalytic reduction reactions.First,we introduce the mechanisms underlying cation effects.We then provide a comprehensive overview of their application in electroreduction reactions.Characterization techniques and theoretical calcula-tion methods for studying cation effects are also discussed.Finally,we address remaining challeng-es and future perspectives in this field.We hope that this review offers fundamental insights and design guidance for utilizing cation effects,thereby advancing their development.

Protective effects of baffles with different positions,row spacings,heights on debris flow impact

The baffle effectively slowed down debris flow velocity,reduced its kinetic energy,and significantly shortened the distance of debris flow movement.Consequently,they are widely used for protection against natural hazards such as landslides and mudslides.This study,based on the threedimensional DEM(Discrete Element Method),investigated the impact of different baffle positions on debris flow protection.Debris flow velocity and kinetic energy variations were studied through single-factor experiments.Suitable baffle positions were preliminarily selected by analyzing the influence of the first-row baffle position on the impact force and accumulation mass of debris flow.Subsequently,based on the selected baffle positions and four factors influencing the effectiveness of baffle protection(baffle position(P),baffle height(h),row spacing(S_(r)),and angle of transit area(α)),an orthogonal design was employed to further explore the optimal arrangement of baffles.The research results indicate that the use of a baffle structure could effectively slow down the motion velocity of debris flows and dissipate their energy.When the baffle is placed in the transit area,the impact force on the first-row baffle is greater than that when the baffle is placed in the deposition area.Similarly,when the baffle is placed in the transit area,the obstruction effect on debris flow mass is also greater than that when the baffle is placed in the deposition area.Through orthogonal experimental range analysis,when the impact on the first row of baffles is used as the evaluation criterion,the importance of each influencing factor is ranked asα>P>S_(r)>h.When the mass of debris flow behind the baffle is regarded as the evaluation criterion,the rank is changed to P>α>S_(r)>h.The experimental simulation results show that the optimal baffle arrangement is:P_(5),S_(r)=16,α=35°,h=9.

Kinetics insights into size effects of carbon nanotubes'growth and their supported platinum catalysts for 4,6-dinitroresorcinol hydrogenation

Size effects are a well-documented phenomenon in heterogeneous catalysis,typically attributed to alterations in geometric and electronic properties.In this study,we investigate the influence of catalyst size in the preparation of carbon nanotube(CNT)and the hydrogenation of 4,6-dinitroresorcinol(DNR)using Fe_(2)O_(3)and Pt catalysts,respectively.Various Fe_(2)O_(3)/Al_(2)O_(3)catalysts were synthesized for CNT growth through catalytic chemical vapor deposition.Our findings reveal a significant influence of Fe_(2)O_(3)nanoparticle size on the structure and yield of CNT.Specifically,CNT produced with Fe_(2)O_(3)/Al_(2)O_(3)containing 28%(mass)Fe loading exhibits abundant surface defects,an increased area for metal-particle immobilization,and a high carbon yield.This makes it a promising candidate for DNR hydrogenation.Utilizing this catalyst support,we further investigate the size effects of Pt nanoparticles on DNR hydrogenation.Larger Pt catalysts demonstrate a preference for 4,6-diaminoresorcinol generation at(100)sites,whereas smaller Pt catalysts are more susceptible to electronic properties.The kinetics insights obtained from this study have the potential to pave the way for the development of more efficient catalysts for both CNT synthesis and DNR hydrogenation.

Effects of Maternal Death on Children Living in the Sagnarigu Municipality

Introduction: The greatest effect of maternal mortality is renowned in children aged 2 - 5 months whose mothers had died. Children whose mothers died due to maternal complications were likely to record a higher mortality in infancy compared to children of surviving mothers. Motherless children mostly suffer a lot due to lack of day-to-day care, isolation, lack of motivation as well as economic cost associated with mother’s death. Thus, the purpose of this study was to ascertain the lives of children whose mothers passed away during childbirth at the Sagnarigu Municipality. Methods: This quantitative cross-sectional study was carried out at the Sagnarigu Municipal. The study recruited 297 respondents. To assess the effects of maternal death on the lives of children, families that experienced maternal death were assessed. The number of pregnancies experienced by the deceased woman, pregnancy-related complaints experienced, determinants of maternal death, number of children alive, and their standard of living were assessed with the aid of a structured questionnaire. Results: The data showed that negligence, illiteracy, poor road access, poverty, ignorance, delays in recognizing the problem, delays in making appropriate decisions, delays in the health facility, delays in giving the appropriate treatments, and traditional beliefs were some of the factors that led to maternal death in the Sagnarigu Municipality. Conclusion: The study concluded that determinants of maternal death in the Sagnarigu Municipal included the following;negligence, illiteracy, poverty, and delays in recognizing the problem. The study findings also demonstrated that the effects of maternal death on children are diverse and cut across different areas of a child’s life including livelihood sustenance, healthcare, education, and emotional and psychological development.

Theoretical study of kinetic isotope effects for vacancy diffusion of impurity in solids

Theoretical studies of the diffusionalisotope effect in solids are still stuck in the 1960s and 1970s.With the development of high spatial resolution mass spectrometers,isotopic data of mineral grains are rapidly accumulated.To dig up information from these data,molecularlevel theoretical models are urgently needed.Based on the microscopic definition of the diffusion coe fficient(D),a new theoretical framework for calculating the diffusional isotope effect(DIE(v))(intermsofD*/D)forvacancy-mediated impurity diffusion in solids is provided based on statistical mechanics formalism.The newly derived equation shows that theDIE(v)can be easily calculated as long as the vibration frequencies of isotope-substituted solids are obtained.The calculatedDIE(v)values of^(199)Au/^(195)Au and^(60)Co/^(57)Co during diffusion in Cu and Au metals are all within 1%of errors compared to the experimental data,which shows that this theoretical model is reasonable and precise.

Review of Sc microalloying effects in Al-Cu alloys

Artificially controlling the solid-state precipitation in aluminum (Al) alloys is an efficient way to achieve well-performed properties,and the microalloying strategy is the most frequently adopted method for such a purpose.In this paper,recent advances in lengthscale-dependent scandium (Sc) microalloying effects in Al-Cu model alloys are reviewed.In coarse-grained Al-Cu alloys,the Sc-aided Cu/Sc/vacancies complexes that act as heterogeneous nuclei and Sc segregation at the θ′-Al_(2)Cu/matrix interface that reduces interfacial energy contribute significantly to θ′precipitation.By grain size refinement to the fine/ultrafine-grained scale,the strongly bonded Cu/Sc/vacancies complexes inhibit Cu and vacancy diffusing toward grain boundaries,promoting the desired intragranular θ′precipitation.At nanocrystalline scale,the applied high strain producing high-density vacancies results in the formation of a large quantity of (Cu Sc,vacancy)-rich atomic complexes with high thermal stability,outstandingly improving the strength/ductility synergy and preventing the intractable low-temperature precipitation.This review recommends the use of microalloying technology to modify the precipitation behaviors toward better combined mechanical properties and thermal stability in Al alloys.

Analysis of level structure and monopole effects in Ca isotopes

Understanding the properties of nuclei near the double magic nucleus^(40)Ca is crucial for both nuclear theory and experiments.In this study,Ca isotopes were investigated using an extended pairing-plus-quadrupole model with monopole corrections.The negative-parity states of^(44)Ca were coupled with the intruder orbital g_(9/2)at 4 MeV.The values of E_(4+)/E_(2+)agree well with experimental trend from^(42)Ca to^(50)Ca,considering monopole effects between νf_(7/2)and νp_(3/2)(νf_(5/2)).This monopole effect,determined from data of^(48)Ca and^(50)Ca,supports the proposed new nuclear magic number N=34 by predicting a high-energy 2^(+)state in^(54)Ca.

Temporal changes in mixing effects on litter decay and nitrogen release in a boreal riparian forest in northeastern China

In riparian forests,litter decay provides essential energy and nutrients for both terrestrial and fluvial ecosystems.Litter mixing effects(LMEs)are crucial in regulating litter decay and nutrient dynamics,yet how LMEs change over time is unclear in riparian forests.In this study,leaf litter of three common species(Alnus sibirica Fisch.ex Turcz,Betula platyphylla Sukaczev,and Betula fruticosa Pall.)were mixed in an equal mass ratio and LMEs were measured for mass and nitrogen(N)remaining in whole litter mixtures over a 3-year period in a boreal riparian forest,northeastern China.LMEs were also assessed for component litter mass and N remaining by separating litter mixtures by species.During the decay of litter mixtures,antagonistic effects on mass and N remaining were dominant after one and two years of decay,whereas only additive effects were observed after three years.LMEs correlated negatively with functional diversity after the first and two years of decay but disappeared after three years.When sorting litter mixtures by species,non-additive LMEs on mass and N remaining decreased over incubation time.Moreover,non-additive LMEs were more frequent for litter of both B.platyphylla and B.fruticosa with lower N concentration than for A.sibirica litter with higher N concentration.These results indicate that incubation time is a key determinant of litter mixing effects during decay and highlight that late-stage litter mixture decay may be predicted from single litter decay dynamics in boreal riparian forests.

Electronic effects on radiation damage inα-iron:A molecular dynamics study

Iron(Fe)-based alloys,which have been widely used as structural materials in nuclear reactors,can significantly change their microstructure properties and macroscopic properties under high flux neutron irradiation during operation,thus,the problems associated with the safe operation of nuclear reactors have been put forward naturally.In this work,a molecular dynamics simulation approach combined with electronic effects is developed for investigating the primary radiation damage process inα-Fe.Specifically,the influence of electronic effects on the collision cascade in Fe is systematically evaluated based on two commonly used interatomic potentials for Fe.The simulation results reveal that both electronic stopping(ES)and electron-phonon coupling(EPC)can contribute to the decrease of the number of defects in the thermal spike phase.The application of ES reduces the number of residual defects after the cascade evolution,whereas EPC has a reverse effect.The introduction of electronic effects promotes the formation of the dispersive subcascade:ES significantly changes the geometry of the damaged region in the thermal spike phase,whereas EPC mainly reduces the extent of the damaged region.Furthermore,the incorporation of electronic effects effectively mitigates discrepancies in simulation outcomes when using different interatomic potentials.

Elucidating solvent effects on the stability of phenoxyl radicals in monohydric alcohols via electron paramagnetic resonance

Research on solvent effects is an important and long-standing topic,but there still is some room,especially for the special solvent effect of fluoroalcohols.In this work,we investigated the stability of phenoxyl radical in monohydric alcohol solvents through in-situ electron paramagnetic resonance detections.The decay behavior of phenoxyl radical showed a reasonable relationship with the mesoscopic structure of alcohols,characterized by smalland wide-angle X-ray scattering.Moreover,the distinct solvent effects of fluoroalcohols were emphasized,and the significant influence of van der Waals distance in the solvents was suggested.Overall,the stability of phenoxyl radical in alcohols was quantified and correlated with the solvent structures.We believe that the established method for stability study on radicals will encourage solvent effect studies on various organic reactions,and the proposed solvent effects in fluoroalcohols may inspire the development of green solvents in both industrial conversions and organic synthesis.