Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal trafficking.However,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this effect.In this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic analysis.The results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer pain.In addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain hypersensitivity.Furthermore,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression.Moreover,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was enhanced.Mechanistically,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F.Additionally,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 methylation.These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions

Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

Responses of growth performance,antioxidant function,small intestinal morphology and mRNA expression of jejunal tight junction protein to dietary iron in yellow-feathered broilers

This study aimed to investigate the dose-effect of iron on growth performance,antioxidant function.intestinal morphology,and mRNA expression of jejunal tight junction protein in 1-to21-d-old yellow-feathered broilers.A total of 7201-d-old yellow-feathered maleb roilers were allocated to 9 treatments with 8 replicate cages of 10 birds per cage.The dietary treatments were consisted of a basal diet(contained 79.6 mg Fe kg^(-1))supplemented with 0,20,40,60,80,160,320,640,and 1,280 mg Fe kg^(-1)in the form of FeSO_(4)·7H_(2)O.Compared with the birds in the control group,birds supplemented with 20mg Fe kg^(-1)had higher average daily gain(ADG)(P<0.0001).Adding 640 and 1,280 mg Fe kg^(-1)significantly decreased ADG(P<0.0001)and average daily feed intake(ADFI)(P<0.0001)compared with supplementation of 20mg Fe kg^(-1).Malondialdehyde(MDA)concentration in plasma and duodenum increased linearly(P<0.0001),but MDA concentration in liver and jejunum increased linearly(P<0.05)or quadratically(P<0.05)with increased dietary Fe concentration.The villus height(VH)in duodenum and jejunum,and the ratio of villus height to crypt depth(V/C)in duodenum decreased linearly(P?0.05)as dietary Feincreased.As dietary Fe increased,the jejunal relative mRNA abundance of claudin-1 decreased linearly(P=0.001),but the jejunal relative mRNA abundance of zona occludens-1(ZO-1)and occludin decreased linearly(P?0.05)or quadratically(P?0.05).Compared with the supplementation of 20 mg Fe kg^(-1),the supplementation of640 mg Fe kg^(-1)or higher increased(P?0.05)MDA concentrations in plasma,duodenum,and jejunum,decreased VH in the duodenum and jejunum,and the addition of 1,280 mg Fe kg^(-1)reduced(P?0.05)the jejunal tight junction protein(claudin-1,ZO-1,occludin)mRNA abundance.In summary,640 mg of supplemental Fe kg^(-1)or greater was associated with decreased growth performance,increased oxidative stress,disrupted intestinal morphology,and reduced mRNA expression of jejunal tight junction protein.

Calmodulins and calmodulin-like proteins-mediated plant organellar calcium signaling networks under abiotic stress

Plant calmodulins(CaMs)and calmodulin-like proteins(CMLs)mediate Ca~(2+)signaling in response to abiotic stresses.Manipulation of this signaling in crops could increase stress tolerance.We review methods for detecting Ca~(2+)signals,regulatory roles of Ca Ms and CMLs,binding targets,and Ca~(2+)networks under abiotic stress in organelles.

Optimizing the Bacillus thuringiensis(Bt)protein concentration in cotton:Coordinated application of exogenous amino acids and EDTA to reduce spatiotemporal variability in boll and leaf toxins

During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for controlling cotton bollworms.Consequently,an experimental strategy was designed in the 2020-2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation.Two Bt cultivars of Gossypium hirsutum,namely the hybrid Sikang 3 and the conventional Sikang 1,were used as test materials.Three treatments were applied at the peak flowering period:CK(the control),T1(amino acids),and T2(amino acids and EDTA).The results show that,in comparison to the CK group,the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments.The maximum levels of increase observed were 67.5%in cotton bolls and 21.7%in leaves.Moreover,the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%.Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism,which are independent of Bt gene expression levels.Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity,while reducing the catabolic enzyme activities,are instrumental in enhancing the Bt protein content.Consequently,the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.

Essential proteins identification method based on four-order distances and subcellular localization information

Essential proteins are inseparable in cell growth and survival. The study of essential proteins is important for understanding cellular functions and biological mechanisms. Therefore, various computable methods have been proposed to identify essential proteins. Unfortunately, most methods based on network topology only consider the interactions between a protein and its neighboring proteins, and not the interactions with its higher-order distance proteins. In this paper, we propose the DSEP algorithm in which we integrated network topology properties and subcellular localization information in protein–protein interaction(PPI) networks based on four-order distances, and then used random walks to identify the essential proteins. We also propose a method to calculate the finite-order distance of the network, which can greatly reduce the time complexity of our algorithm. We conducted a comprehensive comparison of the DSEP algorithm with 11 existing classical algorithms to identify essential proteins with multiple evaluation methods. The results show that DSEP is superior to these 11 methods.

5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.

Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins

Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.

γ-Aminobutyric acid alleviates litchi thaumatin-like protein-induced inflammation and reduces gut microbial translocation

Previous research reported litchi thaumatin-like protein(LcTLP)could lead to inflammation,which is a factor causing the adverse reactions after excessive intake of litchi.As a main amino acid in litchi pulp,γ-aminobutyric acid(GABA)was found with anti-inflammatory effect.Therefore,this study aimed to investigate the effects of GABA on LcTLP-induced inflammation through RAW264.7 macrophages and C57BL mice models.In vitro study showed GABA could effectively regulate the level of inflammatory cytokines(interleukin(IL)-1β,IL-6,IL-10,and prostaglandin E2)and Ca2+in cells,and inhibit the phosphorylation of p65,IκB,p38,c-Jun N-terminal kinase(JNK)and extracellular signal-regulated kinase(ERK).These results indicate GABA alleviated inflammation through nuclear factor-κB and mitogen-activated protein kinase pathway signaling pathways.In vivo experiment was performed to verify the anti-inflammatory effect of GABA,and the results demonstrated that GABA reduced the inflammation and oxidative stress in the liver of LcTLP-treated mice,as it down-regulated the pro-inflammatory cytokines,malondialdehyde,aspartate transferase,and alanine transaminase.The relative expression of phosphorylated p38,JNK and ERK in mice liver with GABA treatment were reduced to 65%,39%and 80%of the control group,respectively.Furthermore,GABA treatment enriched probiotic bacteria and decreased pathogenic bacteria in mice gut,which reveals GABA could effectively reduce the translocation of gut microbiota.

The physiological role of the unfolded protein response in the nervous system

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded proteins.The UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein degradation.It also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum stress.Recent research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous system.Here,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

A novel secreted protein FgHrip1 from Fusarium graminearum triggers immune responses in plants

Fusarium graminearum,the primary pathogenic fungus responsible for Fusarium head blight(FHB)in wheat,secretes abundant chemical compounds that interact with host plants.In this study,a secreted protein FgHrip1,isolated from the culture filtrate of F.graminearum,was found to induce typical cell death in tobacco.The FgHrip1 gene was then cloned and expressed in Escherichia coli.Further bioassay analysis showed that the recombinant FgHrip1 induced early defense induction events,such as reactive oxygen species(ROS)production,callose deposition,and up-regulation of defense-related genes in tobacco.Furthermore,FgHrip1 significantly enhanced immunity in tobacco seedlings against Pseudomonas syringae pv.tabaci 6605(Pst.6605)and tobacco mosaic virus(TMV).FgHrip1-treated wheat spikes also exhibited defense-related transcript accumulation and developed immunity against FHB infection.Whereas the expression of FgHrip1 was induced during the infection process,the deletion of the gene impaired the virulence of F.graminearum.Our results suggest that FgHrip1triggers immunity and induces disease resistance in tobacco and wheat,thereby providing new insight into strategy for biocontrol of FHB.

Surviving winter on the Qinghai-Xizang Plateau:Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri

Changes in protein abundance and reversible protein phosphorylation(RPP)play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes.To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation,we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog,Nanorana parkeri,living on the Qinghai-Xizang Plateau.In total,5170 proteins and 5695 phosphorylation sites in 1938 proteins were quantified.Based on proteomic analysis,674 differentially expressed proteins(438 up-regulated,236 down-regulated)were screened in hibernating N.parkeri versus summer individuals.Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways,whereas lower expressed proteins were mainly involved in metabolic processes.A total of 4251 modified sites(4147 up-regulated,104 down-regulated)belonging to 1638 phosphoproteins(1555 up-regulated,83 down-regulated)were significantly changed in the liver.During hibernation,RPP regulated a diverse array of proteins involved in multiple functions,including metabolic enzymatic activity,ion transport,protein turnover,signal transduction,and alternative splicing.These changes contribute to enhancing protection,suppressing energy-consuming processes,and inducing metabolic depression.Moreover,the activities of phosphofructokinase,glutamate dehydrogenase,and ATPase were all significantly lower in winter compared to summer.In conclusion,our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.

A potential hyphal fusion protein complex with an important role in development and virulence interacts with autophagy-related proteins in Fusarium pseudograminearum

Hyphal fusion(anastomosis)is a common process serving many important functions at various developmental stages in the life cycle of ascomycetous fungi.However,the biological roles and molecular mechanisms in plant pathogenic fungi were widely unknown.In this study,a hyphal fusion protein FpHam-2 was screened from a T-DNA insertion mutant library of Fusarium pseudograminearum,and FpHam-2 interacts with another 2 hyphal fusion protein homologues FpHam-3 and FpHam-4.Each of these 3 genes deletion mutant revealed in similar defective phenotypes compared with the WT and complemented strains,including reduction in growth rate,defects in hyphal fusion and conidiation,more sensitive for cell membrane,cell wall and oxidative stress responses,and decreased in virulence.The yeast two-hybrid assay was used to identify that FpHam-2 interacts with 3 autophagy-related proteins,including FpAtg3,FpAtg28 and FpAtg33.Furthermore,FpHam-2-deletion mutant showed decreased accumulation of autophagic bodies in hypha.In conclusion,FpHam-2,FpHam-3 and FpHam-4 have an essential role for hyphal fusion and regulating the growth,conidiation and virulence in F.pseudograminearum.

Barley Protein LFBEP-C1 from Lactiplantibacillus plantarum dy-1 Fermented Barley Extracts by Inhibiting Lipid Accumulation in a Caenorhabditis elegans Model

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

Regulation of different light conditions for efficient biomass production and protein accumulation of Spirulina platensis

Light plays an important role in the photosynthesis and metabolic process of microalgae.However,how different light conditions regulate the biomass production and protein accumulation of microalgae is mostly unknown.In this study,the influence of different light conditions,including light colors,densities,and light:dark cycles on the cell growth and biochemical composition of Spirulina platensis was symmetrically characterized.Under different colored lights,S.platensis all shows an increase trend within the increased light intensity ranges;however,each showing different optimal light intensities.At the same light intensity,different colored lights show different growth rate of S.platensis following the sequence of red>white>green>yellow>blue.The maximum growth rate and protein accumulation were determined as 21.88 and 5.10 mg/(L·d)when illuminated under red LED.The energy efficiency of different light sources was calculated and ranked as red>white>blue≈green>yellow.Transcriptomic analysis suggests that red light can promote cell growth and protein accumulation by upregulating genes related to photosynthesis,carbon fixation,and C-N metabolism pathways.This study provides a conducive and efficient way to promote biomass production and protein accumulation of S.platensis by regulating light conditions.

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality rate.We aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and CAP.METHODS:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April 2020.Patients were allocated to the DM or non-DM group and paired with propensity score matching.Baseline characteristics and clinical outcomes up to 90 days were evaluated.The primary outcome was the 10-day mortality.Receiver operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical analysis.RESULTS:Among 152 enrolled patients,60 pairs were successfully matched.There was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml vs.median 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of 0.747.The cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,respectively.Multivariate Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with DM.CONCLUSION:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Preliminary study of the role of inner ear proteins in vestibular neuritis

Objective:To evaluate the plasma levels of the otoconial proteins,otoconin-90 and otolin-1,in individuals diagnosed with vestibular neuritis(VN)and determine the feasibility of using these proteins as biomarkers for VN.Methods:In this preliminary study,30 patients diagnosed with VN and 70 healthy individuals were recruited and followed to confirm whether they had benign paroxysmal positional vertigo(BPPV)during the following time.The recorded data included measurements of height,weight,and history of diabetes mellitus or hypertension.Additionally,levels of plasma otoconin-90,and otolin-1 were measured and compared.Results:The plasma concentrations of otoconin-90 and otolin-1 may not be significantly different between patients with VN and healthy controls,nor among patients with BPPV secondary to VN and patients with VN without BPPV.Conclusions:Plasma otoconin-90 and otolin-1 levels may not serve as biomarkers of acute VN episodes or predict BPPV occurrence secondary to VN.