Biomarkers for neuromyelitis optica:a visual analysis of emerging research trends

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity,specificity,and safety for the accurate diagnosis of neuro myelitis optica.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty:a prospective,double-blind,pilot,randomised controlled trial

Background Postoperative sleep disturbance(PSD)is a common and serious postoperative complication and is associated with poor postoperative outcomes.Aims This study aimed to investigate the effect of transcranial direct current stimulation(tDCS)on PSD in older patients undergoing lower limb major arthroplasty.Methods In this prospective,double-blind,pilot,randomised,sham-controlled trial,patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS(a-tDCS)or sham tDCS(s-tDCS).The primary outcomes were the objective sleep measures on postoperative nights(N)1 and N2.Results 116 inpatients were assessed for eligibility,and a total of 92 patients were enrolled;47 received a-tDCS and 45 received s-tDCS.tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups;the respective comparisons were as follows:the promotion of rapid eye movement(REM)sleep time on N1(64.5(33.5-105.5)vs 19.0(0.0,45.0)min,F=20.10,p<0.001)and N2(75.0(36.0-120.8)vs 30.0(1.3-59.3)min,F=12.55,p<0.001);the total sleep time on N1(506.0(408.0-561.0)vs 392.0(243.0-483.5)min,F=14.13,p<0.001)and N2(488.5(455.5-548.5)vs 346.0(286.5-517.5)min,F=7.36,p=0.007);the deep sleep time on N1(130.0(103.3-177.0)vs 42.5(9.8-100.8)min,F=24.4,p<0.001)and N2(103.5(46.0-154.8)vs 57.5(23.3-106.5)min,F=8.4,p=0.004);and the percentages of light sleep and REM sleep on N1 and N2(p<0.05 for each).The postoperative depression and anxiety scores did not differ significantly between the two groups.No significant adverse events were reported.Conclusion In older patients undergoing lower limb major arthroplasty,a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures.However,this benefit was temporary and was not maintained over time.

In-situ electrochemical study on the eff ects of Fe(Ⅲ)on kinetics of pyrite acidic pressure oxidation

Fe(Ⅲ)has been proved to be a more eff ective oxidant than dissolved oxygen at ambient temperature,however,the role of Fe(Ⅲ)in pyrite acidic pressure oxidation was rarely discussed so far.In this paper,in-situ electrochemical investigation was performed using a flow-through autoclave system in acidic pressure oxidation environment.The results illustrated that increasing Fe(Ⅲ)concentrations led to raising in redox potential of the solution,and decreased passivation of pyrite caused by deposition of elemental sulfur.Reduction of Fe(Ⅲ)at pyrite surface was a fast reaction with low activation energy,it was only slightly promoted by rising temperatures.While,the oxidation rate of pyrite at all investigated Fe(Ⅲ)concentrations increased obviously with rising temperatures,the anodic reaction was the rate-limiting step in the overall reaction.Activation energy of pyrite oxidation decreased from 47.74 to 28.79 kJ/mol when Fe(Ⅲ)concentration was increased from 0.05 to 0.50 g/L,showing that the reaction kinetics were limited by the rate of electrochemical reaction at low Fe(Ⅲ)concentrations,while,it gradually turned to be diffusion control with increasing Fe(Ⅲ)concentrations.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression.Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention.Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation.Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological damage.While pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been established.The objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

Comparative transcriptome analysis of sweet corn seedlings under low-temperature stress

Stress induced by low temperature, which represents a widespread environmental factor,strongly affects maize growth and yield. However, the physiological characteristics and molecular regulatory mechanisms of maize seedlings in response to cold remain poorly understood. In this study, using RNA-seq, we investigated the transcriptome profiles of two sweet com inbred lines, "Richao"(RC) and C5, under cold stress. A total of 357 and 455 differentially expressed genes(DEGs) were identified in the RC and C5 lines, respectively, 94 DEGs were detected as common DEGs related to cold response in both genotypes, and a total of 589 DEGs were detected as cold tolerance-associated genes. By combining protein function clustering analysis and significantly enriched Gene Ontology(GO) terms analysis,we suggest that transcription factors may play a dominating role in the cold stress response and tolerance of sweet com. Furthermore, 74 differentially expressed transcription factors were identified, of those many genes involved in the metabolism and regulation of hormones. These results expand our understanding of the complex mechanisms involved in chilling tolerance in maize, and provide a set of candidate genes for further genetic analyses.

In vitro anther culture and Agrobacterium-mediated transformation of the AP1 gene from Salix integra Linn. in haploid poplar(Populus simonii × P. nigra)

A reliable,efficient anther culture system,the dominant technique for generating haploid plants in breeding programs,that can be used for generating transgenic poplar plants has been needed.In the present study,therefore,an anther culture system was developed using isolated mid-and late-uninucleate anthers of poplar(Populus simonii x P.nigra).From a combination of SSR and ploidy analyses,six double haploid and two haploid lines were characterized from 86 plants grown from 16 regenerated anther cultured lines.After 48 months of development,two plant lines from the regenerated plants maintained their haploid level in vitro for over 2 years.A number of haploid plants from the different lines weretransferred to soil.The leaves of these transplants were then used as explants for transformation with the APETALA1(AP1) gene using Agrobacterium tumefaciens.Overexpression of AP1 in haploid poplar induced early flowering with obvious petals when ectopically expressed.To our knowledge,this is the first report on changes in flowering time in AP1-trangenic poplar,which is important for elucidating the regulatory mechanism of tree flower development.

Effects of hurricane forward speed and approach angle on storm surges: an idealized numerical experiment

The effects of hurricane forward speed(V)and approach angle(θ)on storm surge are important and a systematic investigation covering possible and continuous ranges of these parameters has not been done before.Here we present such a study with a numerical experiment using the Finite Volume Community Ocean Model(FVCOM).The hurricane track is simplified as a straight line,such that V andθfully define the motion of the hurricane.The maximum surge is contributed by both free waves and a forced storm surge wave moving with the hurricane.Among the free waves,Kelvin-type waves can only propagate in the down-coast direction.Simulations show that those waves can only have a significant positive storm surge when the hurricane velocity has a down-coast component.The optimal values of V andθthat maximize the storm surge in an idealized semi-circular ocean basin are functions of the bathymetry.For a constant bathymetry,the maximum surge occurs when the hurricane approaches the coast from the normal direction when the free wave generation is minimal;for a stepped bathymetry,the maximum surge occurs at a certain acute approach angle which maximizes the duration of persistent wind forcing;a step-like bathymetry with a sloped shelf is similar to the stepped bathymetry,with the added possibility of landfall resonance when the free and forced waves are moving at about the same velocity.For other cases,the storm surge is smaller,given other parameters(hurricane size,maximum wind speed,etc.)unchanged.

Roles of interleukins in antibacterial immune defense of the brood pouch in the lined seahorse Hippocampus erectus

Seahorse embryos are brooded in the enclosed nutrient-rich environment of the male brood pouch,which may be prone to bacterial infection.The immune responses of interleukin(IL)genes in the brood pouch have not been well studied.We identifi ed 13 interleukins in the lined seahorse Hippocampus erectus.Tissue-specifi c expression analysis revealed increased mRNA expression levels of il-1β,il-18,and il-8 in the brood pouch.When challenged with lipopolysaccharide or Vibrio parahaemolyticus,il-1βand il-18 were active as part of the acute and chronic infl ammatory responses,respectively.Importantly,il-8 may be involved in powerful antibacterial immune responses and may be induced by il-1βand il-18 via a process involving the nuclear factor-κB signaling pathway.These results suggest that il-1β,il-18,and il-8 may play key roles in the antibacterial immune defense of the brood pouch in male seahorses.

Research on Long Stroke Moving Secondary Permanent Magnet Linear Eddy Current Brake

In this paper,a long stroke moving secondary permanent magnet linear eddy current brake is proposed.Without exciting coils,the permanent magnet eddy current brake possesses the advantage of saving copper and better reliability.The topology and operating principle are presented.The mathematical model was derived with the layer theory.The braking force characteristic was analyzed using the finite element method.The structural parameters of the long stroke moving secondary permanent magnet linear eddy current brake were studied by referring the design progress of the other types of eddy current brakes.Finally,a prototype of long stroke moving secondary permanent magnet linear eddy current brake was built and tested,and the experimental result verifies the correctness of the above analysis.

Research on Influence of Motor Parameters on the Negative-Salient Permanent Magnet Synchronous Motor

The d-axis inductance(Ld)of the negative-salient permanent magnet synchronous motor(NSPMSM)is larger than the q-axis inductance(Lq).Compared with the traditional motor,the NSPMSM has the characteristics of a high overload capacity,wide speed range,and preventing permanent magnet demagnetization.Positive d-axis current(id)is applied to control positive reluctance torque when running at base speed.When the motor is running at high speed,a relatively small id can achieve speed expansion and effectively expand the motor flux-weakening range.The use of a magnetic bridge to increase the Ld and a W-type permanent magnet to reduce the Lq is proposed in this article as a novel NSPMSM rotor structure.Firstly,the working principle of the NSPMSM was determined according to the equivalent magnetic circuit.Secondly,using the finite element method,the influence of motor structure on torque and speed performance of NSPMSM was analyzed,and the motor structure was optimized.Thirdly,the effect of the internal power factor angle on the performance of the two motors is analyzed.Finally,the short circuit simulation and analysis verified that the NSPMSM has a stronger short circuit current suppression ability without sacrificing overload ability.

Imprinting, methylation, and expression characterization of the maize ETHYLENE-INSENSITIVE 2-like gene

The endosperm plays essential roles in embryogenesis and seed germination and provides abundant resources for human food and industrial products. Identification of genes regulating the development of the endosperm and elucidation of their functions is of great importance for maize genetics and breeding. This study showed that the genespecific imprinted gene, ETHYLENE-INSENSITIVE 2-like(EIN2-like), is maternally expressed in both endosperm and embryo. The maternally expressed pattern was maintained throughout later seed developmental stages. Bisulfite sequencing using DNA obtained from hybrid endosperm tissues showed that the upstream regions of the alleles of EIN2-like were highly methylated at symmetrical sites(CG and CHG). A differentially methylated region in the upstream part of the maternal allele of EIN2-like was identified and found to be hypomethylated. Expression analysis showed that EIN2-like was highly expressed in the maize endosperm as well as at different stages of cell differentiation(8–12 days after pollination) in the hybrid endosperm. These results suggest that the maternally expressed gene EIN2-like may play crucial roles in the regulation of seed development.

Hematologic toxicity of gemcitabine: a comparison between fixed-dose rate infusion and thirty-minute infusion in the treatment of malignancy

Objective： The aim of the study was to compare the hematologic toxicity of gemcitabine between fixed-dose rate （FDR） infusion and 30-minute standard infusion in the treatment of malignancy. Methods： The 25 malignancy patients confirmed by histopathology or cytology received single-agent gemcitabine or gemcitabine in combination with other chemo- therapeutic agents. These patients were randomly divided into gemcitabine 1000 mg/m2 on dl, d8 at a rate of 10 mg/m2/min arm （FDR arm） or 30 rain arm （standard arm）, every 21 days one cycle. Hematologic toxicity was evaluated at the end of each cycle. Results： The 13 of 25 patients received gemcitabine FDR therapy, a total of 28 cycles was completed, and 32 cycles in the others （12 of 25 patients） with the standard arm. All patients were evaluable for hematologic toxicity. The result showed that the grades 3-4 leucopenia was significantly different between the two arms （14.3% vs 0, P 〈 0.05）, and no significant differences of neutropenia, thrombocytopenia and hemoglobin suppression of grades 3-4 （14.3% vs 3.1%, 10.7% vs 3.1%, 3.6% vs 9.4%, P 〉 0.05, respectively） were observed between the two arms, no grade 4 of hemoglobin suppression was observed. Conclusion： Hematologic toxicity of gemcitabine therapy at a fixed-dose rate for malignancy is tolerable.

Evaluation of Atmospheric Correction Algorithms for Landsat-8 OLI and MODIS-Aqua to Study Sediment Dynamics in the Northern Gulf of Mexico

Suspended particulate matter (SPM) is regarded as an energy source and a water quality indicator in coastal and marine ecosystems. To estimate SPM from ocean color sensors and land observing satellites, an accurate and robust atmospheric correction must be done. We evaluated the capabilities of ocean color and land observing satellite for estimation of SPM concentrations over Louisiana continental shelf in the northern Gulf of Mexico, using the Operational Land Imager (OLI) on Landsat-8, and Moderate Resolution Imaging Spectroradiometer (MODIS) on Aqua. In high turbidity waters, the traditional atmospheric correction algorithms based on near-infrared (NIR) bands underestimate SPM concentrations due to the inaccurate removal of the aerosol contribution to the top of atmosphere signals. Therefore, atmospheric correction in high turbidity waters is a challenge. Four atmospheric correction algorithms were implemented on remote sensing reflectance (Rrs) values to select suitable atmospheric correction algorithms for each sensor in our study area. We evaluated short-wave infrared (SWIR) and NIR atmospheric correction algorithms on Rrs products from Landsat-8 OLI and Management Unit of the North Sea Mathematical Models (MUMM) and SWIR.NIR atmospheric correction algorithms on Rrs products from MODIS-Aqua. SPM was retrieved from a band-ratio SPM-retrieval algorithm for each sensor. Our results indicated that SWIR atmospheric correction algorithm was the suitable algorithm for Landsat-8 OLI and SWIR.NIR atmospheric correction algorithm outperformed MUMM algorithm for MODIS.

Effect of Deformation Conditions on Mechanical Properties of Zr-based Metallic Glasses

In this paper,the effects of different strain rate(1.10-5 s-1,5.10-5 s-1,1.10-4 s-1,5.10-4 s-1,1.10-3 s-1)and aspect ratio(1:1,1.5:1,2:1,2.5:1,3:1)on mechanical properties of Zr-based metallic glasses at room temperature were investigated.The results indicate that as the strain rate increases,the plastic strain and compressive strength of the specimens gradually decrease.The specimen with the strain rate of 1.10-5 s-1 exhibits the higher plastic strain of 10.25%,compressive strength of 2002 MPa and fracture strength of 1999 MPa.In addition,accompanied with the increase in aspect ratio,the plastic strain of the specimens declines from 25.42%to 1.97%,meanwhile,the compressive strength and fracture strength of the specimens also present declining trend.

RDX crystals with high sphericity prepared by resonance acoustic mixing assisted solvent etching technology

In order to obtain high-quality spherical RDX crystal particles,the RDX crystals were suspended in a mixed solvent of cyclohexanone and cyclohexane,subsequently a solvent etching study was carried out under the action of vibration/acoustic flow coupled flow field,which generated by resonance acoustic mixing.The effects of solvent ratio,temperature,acceleration and experiment time on morphology as well as particle size of RDX crystals were studied.Not only were the morphology,particle size distribution and crystal form of RDX crystals determined,but also the thermal decomposition performance and mechanical sensitivity of spherical RDX were examined and discussed.Results indicated that under the process of solvent/non-solvent volume ratio at 1:2,temperature of 40℃,acceleration of 40 g and experiment time of 4 h,α-type RDX crystal with sphericity of 0.92 can be obtained.Furthermore,the median particle size(D_(50))of spherical RDX crystals is 215.8 μm with a unimodal particle size distribution(size span 1.34).For one thing,the thermal decomposition peak temperature of spherical RDX is about 2.5℃ higher than that of raw RDX,and apparent activation energy reaches 444.68 kJ/mol.For another thing,impact sensitivity and friction sensitivity of spherical RDX are 18.18% and 33.33% lower than that of raw RDX,respectively.It demonstrates that safety of spherical RDX under thermal,impact and friction stimuli has been improved.

Identification and Characterization of ZF-HD Genes in Response to Abscisic Acid and Abiotic Stresses in Maize

The zinc finger homeodomain(ZF-HD)genes belong to the homeobox gene family,playing critical roles in flower development and stress response.Despite their importance,however,to date there has been no genome-wide identification and characterization of the ZF-HD genes that are probably involved in stress responses in maize.In this study,24 ZF-HD genes were identified,and their chromosomal locations,protein properties,duplication patterns,structures,conserved motifs and expression patterns were investigated.The results revealed that the ZF-HD genes are unevenly distributed on nine chromosomes and that most of these genes lack introns.Six and two ZF-HD genes have undergone segmental and tandem duplication,respectively,during genome expansion.These 24 ZF-HD transcription factors were classified into six major groups on the basis of protein molecular evolutionary relationship.The expression profiles of these genes in different tissues were evaluated,resulting in producing two distinct clusters.ZF-HD genes are preferentially expressed in reproductive tissues.Furthermore,expression profiles of the 24 ZF-HD genes in response to different kinds of stresses revealed that ten genes were simultaneously up-regulated under ABA,salt and PEG treatments;meanwhile four genes were simultaneously down-regulated.These findings will pave the way for deciphering the function and mechanism of ZF-HD genes on how to implicate in abiotic stress.

EGFR-mutant non-small cell lung cancer patients harboring CDK4 amplification show favorable response to afatinib:Two case reports

To the Editor:Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)show significant efficacy in patients with advanced-stage non-small cell lung cancer(NSCLC)with sensitive EGFR mutations and significantly prolong the survival of these patients.However,drug resistance emerges in most patients.Previous studies indicated that cyclin-dependent kinase 4/6(CDK4/6)gene amplification was one of the resistance mechanisms of the EGFR-TKI osimertinib,weakening its efficacy.Treatment options for EGFR-mutant NSCLC patients with CDK4 amplification are limited to add CDK4 inhibitors.

Fracture development in shale and its relationship to gas accumulation

Shale with high quartz, feldspar and carbonate, will have low Poisson＇s ratio, high Young＇s modulus and high brittleness. As a result, the shale is conducive to produce natural and induced fractures under external forces. In general, there is a good correlation between fracture development in shale and the volume of brittle minerals present. Shale with high TOC or abnormally high pressure has well-developed fractures. Shale fracture development also shows a positive correlation with total gas accumulation and free gas volume, i.e., the better shale fractures are developed, the greater the gas accumulation and therefore the higher the gas production. Fractures provide migration conduits and accumulation spaces for natural gas and formation water, which are favorable for the volumetric increase of free natural gas. Wider fractures in shale result in gas loss. In North America, there is a high success ratio of shale gas exploration and high gas production from high-angle fracture zones in shale. Good natural gas shows or low yield producers in the Lower Paleozoic marine organic matter-rich rocks in the Sichuan Basin are closely related to the degree of fracture development in brittle shales.