Strong biosynthesis and weak catabolism of theanine in new shoots contribute to the high theanine accumulation in Albino/etiolated tea plant(Camellia sinensis)

Tea processed from albino/etiolated tea shoots is favored by consumers because of its high theanine accumulation.To explore why theanine accumulates highly in new shoots of albino/etiolated tea cultivars,we compared theanine content in shoots and roots of albino/etiolated and common green tea cultivars.Results suggested that high theanine accumulation in albino/etiolated tea shoots was likely not caused by higher theanine biosynthesis in roots.Further analyses suggested that CsAlaDC-catalyzed ethylamine biosynthesis and CsGOGAT1-catalyzed glutamate biosynthesis were more active,and CsGGT2-catalyzed theanine catabolism was weaker in new shoots of these albino/etiolated tea plant cultivars.Therefore,the high theanine accumulation in albino/etiolated shoots is probably contributed by the strong theanine biosynthesis and weak catabolism in new shoots.These findings provided more comprehensive insights into the high accumulation of theanine in new shoots of albino/etiolated tea cultivars,and the knowledge can be used in plant breeding for new cultivars with higher theanine accumulation.

GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice

Objective To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism.Methods The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide(LPS).The chondrocytes were divided into the control group,LPS group,LPS+50 nmol/L GW842166X group,and LPS+100 nmol/L GW842166X group.The cytotoxicity of GW842166X was tested using the CCK-8 assay.Western blot,RT-qPCR,and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes.The expression of extracellular matrix molecules was detected by the Western blot,RT-qPCR,and immunofluorescence.Additionally,the activity of NF-κB was checked by the Western blot and immunofluorescence.The mouse Hulth models were generated to examine the in vivo effects of GW842166X on osteoarthritis.Hematoxylin and eosin staining,safranin O/fast green staining,and immunohistochemistry were applied to detect the histological changes.Results GW842166X below 200µmol/L had no cytotoxicity on the mouse chondrocytes.LPS-induced high expression of TGF-β1,IL-10,TNF-α,and IL-6 was significantly reduced by GW842166X.In addition,GW842166X upregulated the expression of aggrecan and collagen type III,which was downregulated after the LPS stimulation.The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment.Furthermore,LPS decreased the IκBαexpression in the cytoplasm and increased the nuclear p65 expression.However,these changes were reversed by the GW842166X pretreatment.Moreover,the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X.Conclusion GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes,thereby inhibiting the progression of osteoarthritis.

Dietary methionine deficiency stunts growth and increases fat deposition via suppression of fatty acids transportation and hepatic catabolism in Pekin ducks

Background:Although methionine(Met),the first-limiting dietary amino acid,has crucial roles in growth and regulation of lipid metabolism in ducks,mechanisms underlying are not well understood.Therefore,the objective was to use dietary Met deficiency to investigate the involvement of Met in lipid metabolism and fat accumulation of Pekin ducks.Methods:A total of 150 male Pekin ducks(15-d-old,558.5±4.4 g)were allocated into 5 groups(6 replicates with 5 birds each)and fed corn and soybean meal-based diets containing 0.28%,0.35%,0.43%,0.50%,and 0.58%Met,respectively,for 4 weeks.Met-deficient(Met-D,0.28%Met)and Met-adequate(Met-A,0.43%Met)groups were selected for subsequent molecular studies.Serum,liver,and abdominal fat samples were collected to assess the genes and proteins involved in lipid metabolism of Pekin ducks and hepatocytes were cultured in vivo for verification.Results:Dietary Met deficiency caused growth depression and excess fat deposition that were ameliorated by feeding diets with adequate Met.Serum triglyceride and non-esterified fatty acid concentrations increased(P<0.05),whereas serum concentrations of total cholesterol,low density lipoprotein cholesterol,total protein,and albumin decreased(P<0.05)in Met-D ducks compared to those in Met-A ducks.Based on hepatic proteomics analyses,dietary Met deficiency suppressed expression of key proteins related to fatty acid transport,fatty acid oxidation,tricarboxylic acid cycle,glycolysis/gluconeogenesis,ketogenesis,and electron transport chain;selected key proteins had similar expression patterns verified by qRT-PCR and Western blotting,which indicated these processes were likely impaired.In vitro verification with hepatocyte models confirmed albumin expression was diminished by Met deficiency.Additionally,in abdominal fat,dietary Met deficiency increased adipocyte diameter and area(P<0.05),and down-regulated(P<0.05)of lipolytic genes and proteins,suggesting Met deficiency may suppress lipolysis in adipocyte.Conclusion:Taken together,these data demonstrated that dietary Met deficiency in Pekin ducks resulted in stunted growth and excess fat deposition,which may be related to suppression of fatty acids transportation and hepatic catabolism.

The Effects of Glucose Load on Catabolism during Remifentanil-Based Anesthesia in Patients with Diabetes Mellitus: A Prospective Randomized Trial

Background: General anesthesia using remifentanil may suppress the unwanted metabolic changes caused by surgical stress including hyperglycemia and ketogenesis. Surgery-related changes in catabolism can be attenuated with low-dose glucose load, without causing hyperglycemia. However, the impact of glucose load in diabetic patients during surgery is unknown. In this study, we investigated the effect of glucose load on catabolism during remifentanil-based anesthesia in patients with diabetes mellitus. Methods: Twenty-nine patients with diabetes mellitus undergoing elective surgery were randomly assigned to receive a glucose load (1.5 mg/kg/min) or not. Plasma levels of glucose, insulin, cortisol, dopamine, adrenaline, noradrenaline, acetoacetic acid, free fatty acid, ketone bodies, 3-hydroxybutyric acid, and 3-methylhistidine/creatinine, a marker of protein catabolism were measured at the start of surgery and 3 h after the start of surgery. Results: Glucose and insulin levels were significantly higher in patients who received a glucose load than in those who did not. Cortisol levels decreased at 3 h after the start of surgery in both groups whereas the levels of catecholamines were unchanged. Acetoacetic acid and total ketone body levels were significantly lower in patients given a glucose load than in those who were not 3 h after the start of surgery. The difference in the 3 methylhistidine/creatinine ratio between the two groups was not significant. Conclusions: The infusion of glucose suppressed lipid catabolism in diabetic patients under remifentanil-based anesthesia during surgery. Our study also suggests that in patients with diabetes mellitus, protein sparing is inhibited by remifentanil-based anesthesia, regardless of the glucose load. Trial registration: the University Hospital Medical Information Network identifier: UMIN000010914.

Effects of Glucose Load on Catabolism during Propofol-Based Anesthesia with Remifentanil in Patients with Diabetes Mellitus: A Prospective Randomized Trial

Background: Perioperative exacerbation of hyperglycemia and insulin resistance is associated with increased complications in patients with diabetes mellitus. We recently reported that glucose load during anesthesia with sevoflurane suppressed lipid catabolism in diabetic patients. In contrast to inhaled anesthetics, propofol solution contains triglycerides, which can be an energy source during surgery. However, the clinical relevance of glucose load under propofol-based anesthesia in diabetic patients is unknown. Therefore, we investigated the effect of intraoperative glucose load on catabolism during propofol-based anesthesia in patients with diabetes mellitus. Methods: Twenty-three patients with diabetes mellitus undergoing elective surgery with propofol-remifentanil-based anesthesia were randomly assigned to receive a glucose load (1.5 mg/kg/ min) or not. Plasma levels of glucose, insulin, cortisol, catecholamines, acetoacetic acid, free fatty acids, ketone bodies, 3-hydroxybutyric acid, and 3-methylhistidine/creatinine, used as a marker for protein catabolism, were measured at the start of surgery and 3 h later. Results: Glucose and insulin levels were significantly higher in patients who received a glucose load than in those who did not. Nonetheless, the levels of cortisol and catecholamines were unchanged during surgery. Similarly, the difference in the levels of markers for lipid as well as protein catabolism was not significant between the groups at 3 h after the start of surgery. Conclusions: Changes in lipid as well as protein catabolism were not altered by glucose load in diabetic patients under propofol-based anesthesia with remifentanil. Our study suggested that continuous infusion of propofol at a clinical dose is sufficient to reduce the requirement for glucose infusion during surgery in patients with diabetes.

The Sucrose Starvation Signal Mediates Induction of Autophagy- and Amino Acid Catabolism-Related Genes in Cowpea Seedling

In higher plants, autophagy is bulk degradation process in vacuole necessary for survival under nutrient-limited conditions and plays important roles in senescence, development and pathogenic response, etc. Cowpea is one of the most important legume crops in semi-aride region, which is highly tolerant to drought stress. Changes of photoassimilate status by drought stress and/or sink-source balance appeared to affect autophagy and senescence of leaf in cowpea. Accordingly, we focused on roles of sucrose signal in autophagy and amino acid recycling in cowpea. Effects of starvation stress on the expression of autophagy-related genes (ATGs) and amino acid catabolism-related genes in cowpea [Vigna unguiculata (L.) Walp] were examined by Reverse transcription-polymerase chain reaction (RT-PCR) and anti-ATG8i specific antibody. Sucrose starvation stress enhanced the expression levels of VuATG8i, VuATG8c and VuATG4 incowpea seedlings. The expressions of amino acid catabolism related genes, such as asparagine synthase (VuASN1), proline dehydrogenase1 (VuProDH) and branched chain amino acid transaminase (VuBCAT2), are also up-regulated under the sucrose starvation. In contrast, high sucrose condition suppressed autophagy and the expressions of ATGs. These results indicate that sucrose starvation stress stimulates both autophagy and amino acid catabolism by regulation of ATGs and VuBCAT2. It is conceivable that sucrose starvation stress enhances autophagy in cowpea, possibly via branched chain amino acid level regulated by the starvation-induced BCAT.

Dysfunction of branded-chain amino acids catabolism in rat cardiac allograft

Objective Allograft vasculopathy ( AV) ,feature of chronic rejection,is a major serious long - term post - operation complication in organ transplantation. The accurate mechanisms for AV have not been definitively established,but extensive basic and clinical studies dem-

Botrytis cinerea-induced F-box protein 1 enhances disease resistance by inhibiting JAO/JOX-mediated jasmonic acid catabolism in Arabidopsis

Jasmonic acid(JA)is a crucial phytohormone that regulates plant immunity.The endogenous JA level is determined by the rates of its biosynthesis and catabolism in plants.The activation of JA biosynthesis has been well documented;however,how plants repress JA catabolism upon pathogen infection remains elusive.In this study,we identified and characterized Botrytis cinerea-induced F-box protein 1(BFP1)in Arabidopsis.The expression of BFP1 was induced by B.cinerea in a JA signaling-dependent manner,and BFP1 protein was critical for plant defense against B.cinerea and plant response to JA.In addition,BFP1 overexpression increased plant defenses against broad-spectrum pathogens without fitness costs.Further experiments demonstrated that BFP1 interacts with and mediates the ubiquitination and degrada-tion of jasmonic acid oxidases(JAOs,also known as jasmonate-induced oxygenases,JoXs),the enzymes that hydroxylate JA to 12OH-JA.Consistent with this,BFP1 affects the accumulation of JA and 12OH-JA during B.cinerea infection.Moreover,mutation of JAo2 complemented the phenotypes of the bfp1 mutant.Collectively,our results unveil a new mechanism used by plants to activate immune responses upon path-ogeninfection:suppressing JA catabolism.

DNA methylation controlling abscisic acid catabolism responds to light to mediate strawberry fruit ripening

Phytohormones,epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined.In this study,bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light,correlating with reduced abscisic acid(ABA) accumulation.Transcription of the key ABA catabolism gene,ABA 8′-hydroxylase FaCYP707A4,was induced in bagged fruit.With light exclusion whole genome DNA methylation levels were up-regulated,corresponding to a delayed ripening process,while DNA methylation levels in the promoter of FaCYP707A4 were suppressed,correlating with increases in transcript and decreased ABA content.Experiments indicated FaCRY1,a blue light receptor repressed in bagged fruit and FaAGO4,a key protein involved in RNA-directed DNA methylation,could bind to the promoter of FaCYP707A4.The interaction between FaCRY1 and FaAGO4,and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter.Furthermore,transient overexpression of FaCRY1,or an increase in FaCRY1 transcription by blue light treatment,increases the methylation level of the FaCYP707A4 promoter,while transient RNA interference of FaCRY1 displayed opposite phenotypes.These findings reveal a mechanism by which DNA methylation influences ABA catabolism,and participates in light-mediated strawberry ripening.

Bioremediation of Textile Azo Dyes Amido Black 10B, Reactive Black 5, Reactive Blue 160 by Lentinus squarrosulus AF5 and Assessment of Toxicity of the Degraded Metabolites

Bioremediation is an eco-compatible and economical approach to counter textile dye menace. The isolated Lentinus squarrosulus AF5 was assessed for decolourization of textile azo dyes, and had shown ~93%, 88% and 70% decolorization of Reactive blue 160 (RB160), Reactive black 5 (RB5) and Amido black 10B (AB10B) respectively. Further analysis using UV-vis, HPLC, and FTIR, 1H NMR had shown the degradation of the dyes. Toxicity analysis of the metabolites was performed using seed germination and plant growth on two agriculturally important plants Guar (Cyamopsis tetragonoloba) and wheat (Triticum aestivum) as well as cytotoxicity analysis using the human keratinocyte cell line (HaCaT). The dye mix appeared inhibitory for seed germination (20% - 40%), whereas metabolites were non-inhibitory for germination. Treatment of HaCaT cells with of dye mix and metabolites led into 45% and ~100% of cell viability of HaCaT cells respectively. Therefore, metabolites following degradation of the dye mix were observed to be non-toxic.

Amino Acid Catabolism in Plants

Amino acids have various prominent functions in plants. Besides their usage during protein biosynthesis, they also represent building blocks for several other biosynthesis pathways and play pivotal roles during signaling processes as well as in plant stress response. In general, pool sizes of the 20 amino acids differ strongly and change dynamically depending on the developmental and physiological state of the plant cell. Besides amino acid biosynthesis, which has already been investigated in great detail, the catabolism of amino acids is of central importance for adjusting their pool sizes but so far has drawn much less attention. The degradation of amino acids can also contribute substantially to the energy state of plant cells under certain physiological conditions, e.g. carbon starvation. In this review, we discuss the biological role of amino acid catabolism and summarize current knowledge on amino acid degradation pathways and their regulation in the context of plant cell physiology.

The Flowering Repressor SVP Confers Drought Resistance in Arabidopsis by Regulating Abscisic Acid Catabolism

Terrestrial plants must cope with drought stress to survive. Under drought stress, plants accumulate the phytohormone abscisic acid （ABA） by increasing its biosynthesis and decreasing its catabolism. However, the regulatory pathways controlling ABA catabolism in response to drought remain largely unclear. Here, we report that the flowering repressor SHORT VEGETATIVE PHASE （SVP） is induced by drought stress and associates with the promoter regions of the ABA catabolism pathway genes CYP707A 1, CYP707A3 and AtBG1, causing decreased expression of CYP7OTA 1 and CYP707A3 but enhanced expression ofAtBG1 inArabidopsis leaves. Loss-of-function mutations in CYP707A 1 and CYP707A3 or overexpression of AtBG1 could rescue the drought-hypersensitive phenotype of svp mutant plants by increasing cellular ABA levels. Collectively, our results suggest that SVP is a central regulator of ABA catabolism and that a regulatory pathway involving SVP, CYP707A1/3, and AtBG1 plays a critical role in plant response to water deficit and plant drought resistance.

Transcriptional Regulation of Lipid Catabolism during Seedling Establishment

Lipid catabolism in germinating seeds provides energy and substrates for initial seedling growth,but how this process is regulated is not well understood.Here,we show that an AT-hook motif-containing nuclear localized(AHL)protein regulates lipid mobilization and fatty acid p-oxidation during seed germination and seedling establishment.AHL4 was identified to directly interact with the lipid mediator phosphatidic acid(PA).Knockout(KO)of AHL4 enhanced,but overexpression(OE)of AHL4 attenuated,triacylglycerol(TAG)degradation and seedling growth.Normal seedling growth of the OE lines was restored by sucrose supplementation to the growth medium.AHL4-OE seedlings displayed decreased expression of genes involved in TAG hydrolysis and fatty acid oxidation,whereas the opposite was observed in AHL4-KOs.These genes contained AHL4-binding cis elements,and AHL4 was shown to bind to the promoter regions of genes encoding the TAG lipases SDP1 and DALL5 and acyl-thioesterase KAT5.These AHL4-DNA interactions were suppressed by PA species that bound to AHL4.These results indicate that AHL4 suppresses lipid catabolism by repressing the expression of specific genes involved in TAG hydrolysis and fatty acid oxidation,and that PA relieves AHL4-mediated suppression and promotes TAG degradation.Thus,AHL4 and PA together regulate lipid degradation during seed germination and seedling establishment.

MYC2, MYC3, and MYC4 function additively in wounding-induced jasmonic acid biosynthesis and catabolism

Jasmonic acid(JA)plays a critical role in plant defenses against insects and necrotrophic fungi.Wounding or lepidopteran insect feeding rapidly induces a burst of JA in plants,which usually reaches peak values within 1 to 2 h.The induced JA is converted to JA-Ile and perceived by the COI1-JAZ co-receptor,leading to activation of the transcription factors MYC2 and its homologs,which further induce JA-responsive genes.Although much is known about JA biosynthesis and catabolism enzymes and JA signaling,how JA biosynthesis and catabolism are regulated remain unclear.Here,we show that in Arabidopsis thaliana MYC2 functions additively with MYC3 and MYC4 to regulate wounding-induced JA accumulation by directly binding to the promoters of genes function in JA biosynthesis and catabolism to promote their transcription.MYC2 also controls the transcription of JAV1 and JAM1,which are key factors controlling JA biosynthesis and catabolism,respectively.In addition,we also found that MYC2 could bind to the MYC2 promoter and self-inhibit its own expression.This work illustrates the central role of MYC2/3/4 in controlling wounding-induced JA accumulation by regulating the transcription of genes involved in JA biosynthesis and catabolism.

Tasselseed5 encodes a cytochrome C oxidase that functions in sex determination by affecting jasmonate catabolism in maize^FA

Maize(Zea mays L.)is a monoecious grass plant in which mature male and female florets form the tassel and ear,respectively.Maize is often used as a model plant to study flower development.Several maize tassel seed mutants,such as the recessive mutants tasselseed1(ts1)and tasselseed2(ts2),exhibit a reversal in sex determination,which leads to the generation of seeds in tassels.The phenotype of the dominant mutant,Tasselseed5(Ts5),is similar to that of ts2.Here,we positionally cloned the underlying gene of Ts5 and characterized its function.We show that the GRMZM2G177668 gene is overexpressed in Ts5.This gene encodes a cytochrome C oxidase,which catalyzes the transformation of jasmonoyl-L-isoleucine(JA-Ile)to 12 OH-JA-Ile during jasmonic acid catabolism.Consistent with this finding,no JA-Ile peak was detected in Ts5 tassels during the sex determination period,unlike in the wild type.Transgenic maize plants overexpressing GRMZM2G177668 exhibited a tassel-seed phenotype similar to that of Ts5.These results indicate that the JA-Ile peak in tassels is critical for sex determination and that the Ts5 mutant phenotype results from the disruption of this peak in tassels during sex determination.

Aerial ammonia exposure induces the perturbation of the interorgan ammonia disposal and branched-chain amino acid catabolism in growing pigs

Aerial ammonia exposure leads to tissue damage and metabolic dysfunction.However,it is unclear how different organs are coordinated to defend against aerial ammonia exposure.Twenty-four pigs were randomly divided into 4 groups,exposed to 0,10,25 or 35 mg/m^(3) ammonia respectively for 25 d.After above 25 mg/m^(3) ammonia exposure,decreased aspartate(P=0.016),glutamate(P=0.030)and increased ornithine(P=0.002)were found in the ammonia-removing liver,and after high ammonia(35 mg/m^(3))exposure,glutamine synthetase(GS)expression was increased(P=0.012).An increased glutamate(P=0.004)and decreased glutaminase(GLS)expression(P=0.083)were observed in the lungs after high ammonia exposure.There was also an increasing trend of glutamine in the kidneys after high ammonia exposure(P=0.066).For branched-chain amino acid(BCAA)catabolism,high ammonia exposure increased BCAA content in both the lungs and muscle(P<0.05),whereas below 25 mg/m^(3) ammonia exposure increased BCAA only in the lungs(P<0.05).The expression of BCAA transaminase(BCAT1/2)and dehydrogenase complex(BCKDHA/B and DBT)were inhibited to a varying degree in the liver,lungs and muscle after above 25 mg/m^(3) ammonia exposure,especially high ammonia exposure.The expression of BCKDH complex and glutamate-glutamine metabolism-related genes were highly expressed in the liver,followed by the lungs and muscle(P<0.01),whereas the BCAT2 expression was highest in the lungs(P=0.002).Altogether,low ammonia exposure sufficed to evoke the urea cycle to detoxify ammonia in the liver.The process of ammonia removal in the liver and potential ability of the lungs to detoxify ammonia were enhanced with increasing ammonia.Furthermore,high ammonia exposure impaired the BCAA catabolism and decreased the transcripts of the BCAA catabolism-related enzymes,resulting in high BCAA content in extrahepatic tissues.Therefore,with aerial ammonia increasing,an increased urea cycle and glutamine synthesis were ammonia defensive strategies,and high ammonia exposure impaired the BCAA catabolism.

Neophaseic acid catabolism in the 90 -hydroxylation pathway of abscisic acid in Arabidopsis thaliana

Abscisic acid(ABA)hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance.Here,we discover a new downstream catabolite of neophaseic acid(neoPA)in the ABA 90-hydroxyl pathway and identify it as epi-neodihydrophaseic acid(epi-neoDPA)by comparing its accurate mass,retention time,and MSn spectra with those of our chemically synthesized epi-neoDPA.Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity.In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1(neoPA reductase 1)identified from Arabidopsis converts neoPA into epi-neoDPA.Sitedirected mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1.Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants,whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines,suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis.

Target-responsive subcellular catabolism analysis for early-stage antibody-drug conjugates screening and assessment

Events including antibody-antigen affinity,internalization,trafficking and lysosomal proteolysis combinatorially determine the efficiency of antibody-drug conjugate(ADC) catabolism and hence the toxicity.Nevertheless,an approach that conveniently identifies proteins requisite for payload release and the ensuing toxicity for mechanistic studies and quality assessment is lacking.Considering the plethora of ADC candidates under development,we developed a target-responsive subcellular catabolism(TARSC) approach that examines ADC catabolism and probes changes in response to targeted interferences of proteins of interest.We firstly applied TARSC to study the commercial T-DM1 and the biosimilar.We recorded unequivocal catabolic behaviors regardless of the absence and presence of the targeted interferences.Their negligible differences in TARSC profiles agreed with their undifferentiated anti-tumoral efficacy according to further in vitro viability and in vivo tumor growth assays,highlighting TARSC analysis as a useful tool for biosimilarity assessment and functional dissection of proteins requisite for ADC catabolism.Additionally,we employed TARSC to investigate the catabolic behavior of a new trastuzumab-toxin conjugate.Collectively,TARSC can not only characterize ADC catabolism at(sub)cellular level but also comprehensively determine which protein targets affect payload release and therapeutic outcomes.Future use of TARSC is thus anticipated in early-stage screening,quality assessment and mechanistic investigations of ADCs.

A retrospective clinical study of sixty-three cases with persistent inflammation immunosuppression and catabolism syndrome

Objective To study the clinical characteristics and prognosis of patients with persistent inflammation immunosuppression and catabolism syndrome(PICS)in ICU.Methods A total of 126 patients admitted to ICU(ICU stay of more than 10 days,age≥18 years)between January 2014 and December 2014 were retrospectively studied.Data were collected from electronic medical records including demographics,underlying disease。

Comparative genomic analysis of Lactobacillus crispatus strains Lc31 and Lc83 with anti-cervical cancer potential by complete genome sequencing

Lactobacillus crispatus is a commonly found species in the urogenital tract(UGT)of healthy females and can also colonize other niches,such as the gastrointestinal tract(GIT).Although its potential protective role in cervical cancer has been reported,the anticancer mechanisms involved are still unclear.In this study,we sequenced and characterized the complete genomes of two L.crispatus strains(Lc31 and Lc83)isolated from the UGT of healthy women of reproductive age.Phylogenetic and phylogenomic analyses of these two strains and 15 other L.crispatus strains with complete genome sequences revealed that strains from the UGT and GIT clustered separately.UGT strains had a larger genome size,higher GC contents,and more protein-coding sequences and insertion sequence(Is)elements,indicating the likelihood of active horizontal gene transfer in this niche.We found a universal presence of genes encoding bacteriocins and the absence of virulence factors and antibiotic resistance genes in UGT strains,suggesting the potential of L.crispatus as a urogenital probiotic.Comparative genomic analysis identified an ula gene cluster responsible for L-ascorbate catabolism exclusively in UGT strains,and carbohydrate fermentation experiments confirmed that this substrate supported the growth of L.crispatus Lc31 and Lc83.Our findings improve the understanding of how the genome determines niche adaptation by L.crispatus,providing a foundation for investigating the mechanisms by which urogenital-derived L.crispatus promotes female health.