Methotrexate combined with methylprednisolone for the recovery of motor function and differential gene expression in rats with spinal cord injury

Methylprednisolone is a commonly used drug for the treatment of spinal cord injury, but high doses of methylprednisolone can increase the incidence of infectious diseases. Methotrexate has anti-inflammatory activity and immunosuppressive effects, and can reduce in- flammation after spinal cord injury. To analyze gene expression changes and the molecular mechanism of methotrexate combined with methylprednisolone in the treatment of spinal cord injury, a rat model of spinal cord contusion was prepared using the PinPointTM preci- sion cortical impactor technique. Rats were injected with methylprednisolone 30 mg/kg 30 minutes after injury, and then subcutaneously injected with 0.3 mg/kg methotrexate 1 day after injury, once a day, for 2 weeks. TreadScan gait analysis found that at 4 and 8 weeks after injury, methotrexate combined with methylprednisolone significantly improved hind limb swing time, stride time, minimum longitudinal deviation, instant speed, footprint area and regularity index. Solexa high-throughput sequencing was used to analyze differential gene ex- pression. Compared with methylprednisolone alone, differential expression of 316 genes was detected in injured spinal cord treated with methotrexate and methylprednisolone. The 275 up-regulated genes were mainly related to nerve recovery, anti-oxidative, anti-inflammatory and anti-apoptotic functions, while 41 down-regulated genes were mainly related to proinflammatory and pro-apoptotic functions. These results indicate that methotrexate combined with methylprednisolone exhibited better effects on inhibiting the activity of inflammatory cytokines and enhancing antioxidant and anti-apoptotic effects and thereby produced stronger neuroprotective effects than methotrexate alone. The 316 differentially expressed genes play an important role in the above processes.

Microbiome Engineering:A Promising Approach to Improve Coral Health

The world’s coral reefs are threatened by the cumulative impacts of global climate change and local stressors.Driven largely by a desire to understand the interactions between corals and their symbiotic microorganisms,and to use this knowledge to eventually improve coral health,interest in coral microbiology and the coral microbiome has increased in recent years.In this review,we summarize the role of the coral microbiome in maintaining a healthy metaorganism by providing nutrients,support for growth and development,protection against pathogens,and mitigation of environmental stressors.We explore the concept of coral microbiome engineering,that is,precise and controlled manipulation of the coral microbiome to aid and enhance coral resilience and tolerance in the changing oceans.Although coral microbiome engineering is clearly in its infancy,several recent breakthroughs indicate that such engineering is an effective tool for restoration and preservation of these valuable ecosystems.To assist with identifying future research targets,we have reviewed the common principles of microbiome engineering and its applications in improving human health and agricultural productivity,drawing parallels to where coral microbiome engineering can advance in the not-too-distant future.Finally,we end by discussing the challenges faced by researchers and practitioners in the application of microbiome engineering in coral reefs and provide recommendations for future work.

Future therapies for pancreatic carcinoma:Insights into cancer precision medicine

Pancreatic carcinoma(PC)has one of the highest rates of cancer-related death worldwide.Except for surgery,adjuvant chemotherapy,chemoradiotherapy,and immunotherapy have shown various efficacies depending on the stage of the patient.We read the review“Current and emerging therapeutic strategies in pancreatic cancer:Challenges and opportunities”and offer some opinions that may improve its precision and completeness.This review presents a map of appropriate therapies for PC at different stages.Based on the clinical trial outcomes mentioned in the review,we evaluated the potential therapeutic options for PC and helped explain the contradictory efficacy between different programmed cell death protein 1/programmed cell death ligand 1 clinical trials,which may have resulted from the unique features of PC.Although R0 resection and adjuvant chemotherapy are still the gold standards for PC,new modalities,with or without clinical validation,are needed to establish more specific and precise treatments for PC.

Clinical outcomes and 5-year follow-up results of keratosis pilaris treated by a high concentration of glycolic acid

BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation.Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes.It also promotes skin metabolism and accelerates the melanin metabolism.The therapeutic effect is related to the glycolic acid concentration.AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris,and to observe the outcomes at 5-year of follow-up.METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites.High concentrations of glycolic acid(50%or 70%)were applied to a circular area(d=8 cm,S=50 cm2)and repeated four times,on days 0,20,40 and 60.Before each treatment and 20 d after the last treatment,on days 0,20,40,60,and 80 and at a 5-year follow-up,The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined.At the same time,the participants provided subjective evaluations of treatment efficacy and safety.RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site,on days 20,40,60 and 80,which were 8%,12%,36%,and 60%,respectively.Compared with day 0,each difference was significant(P<0.05).Compared with day 0,differences in melanin content(M)in the skin and skin lightness(L)on days 40,60 and 80,the were statistically significant(P<0.05);skin hemoglobin content(E)on days 60 and 80 was statistically different as compared with before treatment(P<0.05).There were no significant differences in the number of keratotic papules,M,L,and E in 9 participants at the 5-year follow-up compared with before treatment(P>0.05%).CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris.The treatment was relatively safe,but there was no significant difference at the 5-year follow-up compared to before treatment.

Chinese herbal medicine combined with Western medicine for Mycoplasma pneumoniae pneumonia in children:An overview of systematic reviews

Objective:To summarize the characteristics and evaluate the quality of the methodology and evidence within systematic reviews(SRs)of Chinese herbal medicine(CHM)for Mycoplasma pneumoniae pneumonia(MPP)inchildren.Methods:SRs of randomized controlled trials were searched using PubMed,the Cochrane Library,Embase,the Chinese National Knowledge Infrastructure Databases(CNKI),the Chinese Scientific Journals Database(VIP),Wanfang,and the SinoMed Database.SRs on the use of CHM alone or in combination with Western medications for MPP in children were included.The study compared the effects of Western medicine alone with those of CHM.The evidence quality using the A Measurement Tool to Assess Systematic Reviews(AMSTAR)2,the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020,and the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)criteria.The primary indicators were the total effective rate,fever subsidence time,and cough disappearance time.The secondary outcomes were pulmonary rale disappearance time,average hospitalization time,lung X-ray infiltrate disappearance time,immunological indices,and inflammatory cytokine levels.Results:Twelve relevant SRs were included;75%(9/12)were assessed as very low quality,and 25%(3/12)Were rated as low quality using the AMSTAR 2 criteria.According to the PRISMA 2020 checklist,the average SR score was 20.3 out of a 27 point maximum.In all SRs,CHM demonstrated improvement in symptoms and signs among children with MPP.The evidence quality using the GRADE criteria ranged from"very low"(>50%)to"moderate"(<5%).The most common downgrading factor was imprecision,followed by publication bias and inconsistency.Conclusion:This overview highlights the limited quality of the methodology and evidence of the included SRs.Although the included studies showed the beneficial effects of CHM on MPP in children,it was difficult to draw firm conclusions owing to methodological flaws.

康柏西普治疗湿性年龄相关性黄斑变性患者应答反应的临床观察

目的:观察康柏西普治疗湿性年龄相关性黄斑变性(wARMD)患者产生不同应答反应的临床特点及影响因素。方法:回顾性分析2018-01/09于我院行康柏西普玻璃体腔注射(3+PRN)的wARMD患者56例62眼的临床资料。治疗前后均进行最佳矫正视力(BCVA)和光学相干断层扫描(OCT)检查,根据注射3次后1mo BCVA情况评估应答反应并进行分组,BCVA提高≥5个字母者33例35眼纳入有应答组,余23例27眼纳入无应答组,分析两组患者治疗前后BCVA、中心视网膜厚度(CRT)情况及相关资料。结果:注射3次后1mo,有应答组患者BCVA从基线时41.83±7.92个字母提高到52.52±10.61个字母(t=-6.883,P=0.02),无应答组患者BCVA从基线时43.65±10.42个字母提高到44.18±8.47个字母(t=0.471,P=0.684),且治疗后两组患者CRT均较基线有不同程度下降(F=31.47、27.28,均P<0.01)。基线时,有应答组患者中黄斑中心凹下椭圆体带较完整者比例(69%)明显多于无应答组(7%),存在视网膜下液者比例(86%)高于无应答组(44%),存在视网膜内液者比例(31%)低于无应答组(81%)(均P<0.05),但两组患者存在色素上皮脱离者比例无差异(77%vs 59%,P>0.05)。结论:康柏西普可有效减少wARMD患者视网膜下积液和视网膜内积液,不同程度改善患者视力,视网膜外层结构(尤其是椭圆体带)的完整性及存在视网膜下积液的患者治疗后应答反应较好,而存在视网膜内积液患者治疗后应答反应不佳。

人工智能支持下的课堂教学评价模型研究

随着人工智能技术的飞速发展及其在课堂教学中的广泛应用,传统的课堂评价模式已不能满足需求,而融合人工智能的相关评价方法仍然存在精确度有偏差、评价内容单一等问题,亟待综合多种因素,开展人机协同以促进课堂教学评价向智能化方向发展。依托人工智能技术构建的课堂教学评价模型,包括智能课堂教学环境、课堂观察方法与技术、课堂数据采集、人工智能支持的课堂教学分析与可视化、教研员解读、教师反思等六个要素,涵盖人工智能课堂教学评价的环境、数据、角色与流程,具备机器、人为参与或反馈等多回路特征,以及促进人工智能技术成长的可行模式,广泛适用于多种智能化教学环境。该模型在实际课堂教学中得以验证,实现课堂智能化教学评价,为课堂教学评价与教师研修评价新范式的提出提供参考。

A new nine-membdered lactone from a marine fungus Cladosporium sp.F14

A new nine-membered lactone,cladospolide E（1）,was isolated from a culture broth of a marine fungus Cladosporium sp.F14. The structure of compound 1 was determined on the basis of extensive spectroscopic analysis,including 1D and 2D NMR data.

Long-term clinical effects of intravitreal injections of conbercept for the treatment of choroidal neovascularization in patients with pathological myopia

AIM:To observe the long-term clinical efficacy of intravitreal injections of conbercept,a novel vascular growth factor inhibitor,for the treatment of pathological myopia choroidal neovascularization(PM-CNV).METHODS:A total of 67 eyes(from 67 patients;mean age,54.90±12.7y)with PM-CNV were retrospectively researched.Based on the different schemes used for the administration of the drug,the patients were divided into two groups:group A(n=35;average age,53.31±13.6y;average diopter,9.25±1.72 D),which received only one injection of pro re nata(PRN;1+PRN regimen),and group B(n=32;average age,56.49±11.8y;average diopter,9.63±2.24 D),which received one injection per month for 3mo(3+PRN regimen).Best-corrected visual acuity(BCVA)analysis,intraocular pressure(IOP)examination,slit-lamp microscopy,fundus examination and optical coherence tomography were per formed at each follow-up.The recurrence and treatment times of CNV were recorded.The patients were followed up for at least 12mo.RESULTS:The BCVA was increased in 29 eyes(82.9%)in group A and 30 eyes(93.75%)in group B;no increase or decrease was observed in 6(17.1%)and 2(6.25%)eyes in groups A and B,respectively.The BCVA(log MAR)values before treatment(0.67±0.48 and 0.71±0.56)were significantly higher than those 12mo after treatment(0.31±0.26 and 0.33±0.17)in groups A and B,respectively(P<0.05).The mean central macular thickness(CMT)values had significantly decreased from 346.49±65.99 and 360.10±82.31μm at baseline to 257.29±40.47 and 251.97±48.26μm in groups A and B,respectively,after 12mo of treatment.A total of 21 eyes in group A needed reinjection(60%;average number of injections,2.51±0.98);the corresponding values in group B were 6 eyes(18.75%;average number of injections,3.74±1.22).There were no adverse ocular and systemic complications during the treatment and follow-up.CONCLUSION:Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity,reduce macular edema and reduce the level of CMT in patients with PM-CNV.The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen,but requires more treatment.However,both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.

Interactions of Microplastics and Methane Seepage in the Deep-Sea Environment

Microplastics(MPs)are important exempla of the Anthropocene and are exerting an increasing impact on Earth’s carbon cycle.The huge imbalance between the MPs floating on the marine surface and those that are estimated to have been introduced into the ocean necessitates a detailed assessment of marine MP sinks.Here,we demonstrate that cold seep sediments,which are characterized by methane fluid seepage and a chemosynthetic ecosystem,effectively capture and accommodate small-scale(<100μm)MPs,with 16 types of MPs being detected.The abundance of MPs in the surface of the sediment is higher in methane-seepage locations than in non-seepage areas.Methane seepage is beneficial to the accumulation,fragmentation,increased diversity,and aging of MPs.In turn,the rough surfaces of MPs contribute to the sequestration of the electron acceptor ferric oxide,which is associated with the anaerobic oxidation of methane(AOM).The efficiency of the AOM determines whether the seeping methane(which has a greenhouse effect 83 times greater than that of CO_(2)over a 20-year period)can enter the atmosphere,which is important to the global methane cycle,since the deep-sea environment is regarded as the largest methane reservoir associated with natural gas hydrates.

Effect of the structure of backward orifices on thejet performance of self-propelled nozzles

Self-propelled nozzle is a critical component of the radial jet drilling technology.Its backward orifice structure has a crucial influence on the propulsive force and the drilling performance.To improve the working performance of the nozzle,the numerical simulation model is built and verified by the experimental results of propulsive force.Then the theoretical model of the energy efficiency and energy coefficient of the nozzle is built to reveal the influence of the structural parameters on the jet performance of the nozzle.The results show that the energy efficiency and energy coefficient of the backward orifice increase first and then decrease with the angle increases.The energy coefficient of forward orifice is almost constant with the angle increases.With the increase in the number and diameter,energy efficiency and energy coefficient of the forward orifice gradually decrease,but the backward orifice energy coefficient first increases and then decreases.Finally,it is obtained that the nozzle has better jet performance when the angle of backward orifice is 30°,the number of backward orifice is 6,and the value range of diameter is 2-2.2 mm.This study provides a reference for the design of efficiently self-propelled nozzle for radial jet drilling technology.

The role of biocrusts in nitrogen cycling on the tropical reef islands,South China Sea

Harboring polyextremotolerant microbial topsoil communities,biological soil crusts(biocrusts)occur across various climatic zones,and have been well studied in the terrestrial drylands.However,little is known about the functional metabolic potential of microbial communities involved in the biogeochemical processes during the early succession of biocrusts on the tropical reef islands.We collected 26 biocrusts and bare soil samples from the Xisha Islands and Nansha Islands,and applied a functional gene array(GeoChip 5.0)to reveal nitrogen(N)cycling processes involved in these samples.Both physicochemical measurement and enzyme activity assay were utilized to characterize the soil properties.Results revealed the composition of N-cycling functional genes in biocrusts was distinct from that in bare soil.Additionally,microorganisms in biocrusts showed lower functional potential related to ammonification,denitrification,N assimilation,nitrification,N fixation,and dissimilatory nitrate reduction to ammonium compared to bare soils.Although the abundance of nifH gene was lower in biocrusts,nitrogenase activity was significantly higher compared to that in bare soils.Precipitation,soil physicochemical properties(i.e.,soil available copper,soil ammonia N and pH)and soil biological properties(i.e.,β-glucosidase,fluorescein diacetate hydrolase,alkaline protease,urease,alkaline phosphatase,catalase and chlorophyll a)correlated to the N-cycling functional genes structure.Nitrate N and ammonia N were more abundant in biocrusts than bare soil,while pH value was higher in bare soil.Our results suggested biocrusts play an important role in N-cycling in coral sand soil,and will be helpful in understanding the development and ecological functions of biocrusts on tropical reef islands.

Alpha-beta chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant Staphylococcus aureus

Staphylococcus aureus(S.aureus)are frequently encountered for both nosocomial infections and community acquired infections,with special concerns on the quick emergence of methicillin resistant S.aureus(MRSA)[1,2].Antibiotics are used extensively to treat these infections[2].However,antimicrobial resistance has been a tremendous challenge against current antibiotic and calls for urgent actions to explore novel antimicrobial agents that are active against MRSA and are less susceptible to antimicrobial resistance than do conventional antibiotics[3–13].Encouraged by the low propensity for microbes to develop antimicrobial resistance,host defense peptides(HDPs)and their synthetic mimics were actively studied[3,4,14–34].Although peptidyl mimics of HDP have variable structures,many of them involved multiple copies ofα-L-lysine to introduce into the molecules positive charges that were critical for the antimicrobial activity[35,36].

Ammonia in urban atmosphere can be substantially reduced by vehicle emission control:A case study in Shanghai, China

To investigate the impact of emission controls on ammonia(NH_(3)) pollution in urban atmosphere, observation on NH_(3)(1 hr interval) was performed in Shanghai before, during and after the 2019 China International Import Expo (CIIE) event, along with measurements on inorganic ions, organic tracers and stable nitrogen isotope compositions of ammonium in PM_(2.5). NH_(3)during the CIIE period was 6.5±1.0μg/m^(3), which is 41% and 32% lower than that before and after the event, respectively. Such a decrease was largely ascribed to the emission controls in nonagricultural sources, of which contribution for measured NH_(3)in control phase abated by ~20% compared to that during uncontrol period. Molecular compositions of PAHs and hopanes further suggested a dominant role of the reduced vehicle emissions in the urban NH_(3)abatement during the CIIE period. Our results revealed that vehicle exhaust emission control is an effective way to mitigate NH_(3)pollution and improve air quality in Chinese urban areas.

Significant coal combustion contribution to water-soluble brown carbon during winter in Xingtai, China: Optical properties and sources

To understand the characteristics of atmospheric brown carbon(BrC),daily PM2.5 samples in Xingtai,a small city in North China Plain(NCP),during the four seasons of 2018-2019,were collected and analyzed for optical properties and chemical compositions.The light absorption at 365 nm(abs λ=365 nm)displayed a strong seasonal variation with the highest value in winter(29.0±14.3 M/m),which was 3.2∼5.4-fold of that in other seasons.A strong correlation of abs λ=365 nm with benzo(b)fluoranthene(BbF)was only observed in winter,indicating that coal combustion was the major source for BrC in the season due to the enhanced domestic heating.The mass absorbing efficiency of BrC also exhibited a similar seasonal pattern,and was found to correlate linearly with the aerosol pH,suggesting a positive effect of aerosol acidity on the optical properties and formation of BrC in the city.Positive matrix factorization(PMF)analysis further showed that on a yearly basis the major source for BrC was biomass burning,which accounted for 34% of the total BrC,followed by secondary formation(26.7%),coal combustion(21.3%)and fugitive dust(18%).However,the contribution from coal combustionwas remarkably enhanced in winter,accounting for∼40%of the total.Our work revealed that more efforts of“shifting coal to clean energy”are necessary in rural areas and small cities in NCP in order to further mitigate PM2.5 pollution in China.

Effects of adalimumab and secukinumab on comorbidities associated with metabolism in patients with plaque psoriasis

To the Editor:Psoriasis is often associated with comorbidities such as cardiovascular diseases,obesity,and metabolic syndrome(MS).However,the prevalence of abovementioned diseases in Chinese patients with plaque psoriasis is still unknown.Recently,biologics such as tumor necrosis alpha inhibitors,interleukin-17A inhibitors have been successfully used in the treatment of plaque psoriasis.However,the effects of biological treatment on comorbidities associated with metabolism are still controversial.Study on the relationship between the comorbidities associated with metabolism and plaque psoriasis and the effects of biologics are necessary.

Effects of secukinumab and adalimumab on serum uric acid level in patients with plaque psoriasis

Background:Psoriasis is a chronic systemic inflammatory disease,and hyperuricemia is a common comorbidity in patients with psoriasis.However,there are limited reports on the relationship between serum uric acid levels and biological treatment efficacy.The purposes of this study were to compare the differences in serum uric acid levels between patients with psoriasis and healthy controls and analyze the risk of hyperuricemia.Methods:A total of 196 patients with psoriasis and 191 age-and sex-matched healthy controls were enrolled in this retrospective cohort study.One hundred and twenty-seven patients with severe psoriasis were treated with biologics.Sixty-eight patients received adalimumab,and 59 patients received secukinumab.Serum uric acid levels were measured at baseline,week 24,and week 48 of treatment.Results:Patients with psoriasis had higher serum uric acid levels than healthy controls(6.4±1.7 mg/dL vs.5.7±1.5 mg/dL,P<0.001).Hyperuricemia was found in 33.7%(66/196)of patients with psoriasis,which was significantly higher than that in healthy controls(13.1%[25/191],P<0.001).Serum uric acid levels and hyperuricemia were not related to the severity of psoriasis(P>0.05).No significant changes in serum uric acid levels and hyperuricemia were observed following adalimumab treatment(P>0.05).The serum uric acid level in patients treated with secukinumab was 6.7±1.6 mg/dL at week 24,which was not statistically different from that at baseline(6.6±1.4 mg/dL,P=0.885).Serum uric acid levels were significantly decreased at week 48(6.3±1.5 mg/dL vs.6.6±1.4 mg/dL,P=0.007)in patients treated with secukinumab.Secukinumab had no significant effect on hyperuricemia either(P>0.05).Conclusions:The serum uric acid levels and prevalence of hyperuricemia in patients with psoriasis were significantly higher than those in healthy controls.Secukinumab treatment for 48 weeks successfully decreased serum uric acid levels in patients with psoriasis,whereas adalimumab had no significant effect on serum uric acid levels.

Bio-inspired Polyimine Copolymers： Facial Integration with High Content Variability and Extremal Transitions of Mechanical Properties

Natural composites have inspired the fabrication of various biomimetic composites that have achieved enhancement on certain mechanical performance. Herein, a facial approach enabled by recent advances in polyimine chemistry has been developed to fabricate bio-inspired hard-soft-integrated copolymers from two polyimines （i.e. PI-H and PI-S） with hardness differential. Subsequent evaluations of multiple mechanical properties on the bio-inspired copolymers with PI-S contents of full-range variability （0 wt%-100 wt%） have revealed extremal transitions for friction coefficients, impact strengths and tensile moduli. More interestingly, the minimum points of friction coefficients show a deformation-resisting response toward the change of applied loads, but not for the altered sliding speeds, suggesting a more significant role of load in determining the optimal anti-friction composition of the hard-soft integrated copolymers. These trends have been further corroborated by scanning electron microscopy of the worn specimens. Together these results have demonstrated that full-range extremal tran- sitions exist on multiple mechanical properties for hard-soft-integrated copolymers, providing valuable insights to the design and fabrication of composite polymers for many applications. The polyimine-based approach outlined here also affords a convenient method to tune the ratio of two components in the copolymers within the full range of 0 wt%-100 wt%, enabling quick integration with high content variability.

A Decision Framework for Automatic Guided Vehicle Routing Problem with Traffic Congestions

Automatic guided vehicles are widely used in various types of warehouses including the automated container terminals.This paper provides a decision framework for port managers to design and schedule automatic guided vehicle routing plans under time-varying traffic conditions.A large number of computational experiments on a grid graph are conducted to validate the efficiency of the proposed decision framework.We also proposed one efficient queueing rule in automatic guided vehicle routing scheduling.Although the complexity of the problem is high,computational results show that our proposed decision framework can provide high quality solutions within a relatively short computation time.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression

Background:Late-onset depression(LOD)and early-onset depression(EOD)exhibit different pathological mechanisms and clinical phenotypes,including different extents of olfactory dysfunction.However,the brain abnormalities underlying the differences in ol-factory dysfunction between EOD and LOD remain unclear.Objective:The aim of this study was to compare the functional connectivity(FC)patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function.Methods:One hundred and five patients with EOD,101 patients with LOD and 160 normal controls(NCs)were recruited for the present study.Participants underwent clinical assessment,olfactory testing,cognitive assessments,and magnetic resonance imaging.Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC.Results:Patients with LOD exhibited decreased odor identification(OI)compared with patients with EOD and NCs.The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest(the piriform cortex,lateral entorhinal cortex,and orbital-frontal cortex).Additionally,these abnormal olfactory FCs were associated with decreased cognitive function scores and OI,and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI.Conclusion:Overall,patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD,and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment.The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.