Predictive performance of triglyceride glucose index (TyG index) to identify glucose status conversion: a 5-year longitudinal cohort study in Chinese pre-diabetes people.

OBJECTIVE: Triglyceride glucose index (TyG index) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG and regression from prediabetes to normoglycemia remains to be elucidated. METHODS: This retrospective cohort study involved 25,248 subjects with prediabetes at baseline conducted from 2010 to 2016. A Cox proportional hazard regression model was designed to evaluate the role of TyG in identifying people at converting from prediabetes to normoglycemia. Cox proportional hazards regression with cubic spline functions and smooth curve fitting was used to dig out the nonlinear relationship between them. Detailed evaluations for TyG were also performed using sensitivity and subgroup analyse. RESULTS: Among the included prediabetes subjects (n = 25,248), the mean age was 49.27 ± 13.84 years old, and 16,701 (66.15%) were male. The mean TyG was 8.83 ± 0.60. The median follow-up time was 2.96 ± 0.90 years. 11,499 (45.54%) individuals had a final diagnosis of normoglycemia. After adjusting for covariates, TyG was negatively affecting the results of glucose status conversion in prediabetes people (HR 0.895, 95% CI 0.863, 0.928). There was a nonlinear connection between TyG and normoglycemia in prediabetes people, and the inflection point was 8.88. The effect sizes (HR) on the left and right sides of the inflection point were 0.99 (0.93, 1.05) and 0.79 (0.74, 0.85), respectively. Sensitivity analysis confirmed the robustness of these results. Subgroup analysis showed that TyG was more strongly associated with incident glucose status conversion in male, BMI ≥ 25. In contrast, there was a weaker relationship in those with female, BMI < 25. CONCLUSION: Based on sample of subjects evaluated between 2010 and 2016, TyG index appears to be a promising marker for predicting normoglycemic conversion among prediabetes people in China. This study demonstrates a negative and non-linear association between TyG and glucose status conversion from prediabetes to normoglycemia. TyG is strongly related to glucose status conversion when TyG is above 8.88. From a therapeutic point of view, it is meaningful to maintain TyG levels within the inflection point to 8.88.

Ejection dynamics of spherically confined active polymers through a small pore.

Using Brownian dynamics simulations, we study the ejection dynamics of spherically confined active polymers through a small pore. Although the active force can provide a driving force other than the entropy drive, it also causes the collapse of the active polymer, which in turn reduces the entropy drive. Thus, our simulation results confirm that the active polymer's ejection process can be divided into three stages. In the first stage, the influence of the active force is small, and the ejection is mainly an entropy-driven process. In the second stage, the ejection time satisfies the scaling relationship with the chain length, and the value of obtained scaling exponent is less than 1.0, indicating that the active force accelerates the ejection process. In the third stage, the scaling exponent is maintained at about 1.0, where the active force dominates the ejection process, and the ejection time is inversely proportional to the Péclet number. Furthermore, we find that the ejection velocity of the trailing particles has significant differences at different stages and is the core factor of the ejection mechanism at different stages. Our work helps us understand this non-equilibrium dynamic process and enhances our prediction of the relevant physiological phenomena.

Profiling the oral microbiomes in patients with Alzheimer's disease.

OBJECTIVES: To analyse the characteristics of the oral microbiomes and expected to find biomarkers about Alzheimer's disease (AD). SUBJECTS AND METHODS: AD patients (n = 26) and cognitive intact people (n = 26) were examined for cognition, depression, oral health and collected saliva and gingival crevicular fluid (GCF) in the morning. Full-length 16S rRNA gene was amplified and sequencing was performed using the PacBio platform. RESULTS: The predominant bacterium of salivary microbiome and periodontal microbiome from AD patients was Streptococcus oralis and Porphyromonas gingivalis, respectively. With respect to ß diversity analysis, there was a significance difference in periodontal microbiome between AD patients and cognitively intact subjects. The relative abundance of Veillonella parvula significantly increased in oral microbiomes from AD patients. Interestingly, the dominant species were different between early-onset AD and late-onset AD patients. Moreover, the predominant species were changed as the clinical severity of AD. Furthermore, the correlation analysis revealed that V. parvula was associated with AD in both saliva and GCF and that P. gingivalis was associated with AD only in GCF. CONCLUSIONS: In this study, the microbiome community of oral microbes was altered in AD patients and periodontal microbiome was sensitive to cognition changes. Moreover, V. parvula and P. gingivalis were associated with AD.

Ruania rhizosphaerae sp. nov., a novel actinobacterium isolated from rhizosphere of Suaeda aralocaspica.

A Gram-stain-positive, non-motile and short rod-shaped actinobacterium, designated strain LNNU 22110T, was isolated from the rhizosphere soil of the halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze, which collected in Xinjiang, north-west China. Growth occurred at 10-45 °C, pH 6.0-10.0 and in the presence of 0-11 % NaCl (w/v). Based on the results of 16S rRNA gene sequence phylogenetic analyses, strain LNNU 22110T belonged to the genus Ruania and had 97.5 and 95.5 % sequence similarity to Ruania alba KCTC 19413T and Ruania albidiflava CGMCC 4.3142T, respectively. The digital DNA-DNA hybridization relatedness values between strain LNNU 22110T and R. alba KCTC 19413T and R. albidiflava CGMCC 4.3142T were 23.2 and 19.9 %, respectively. The highest average nucleotide identity value between strain LNNU 22110T and its closest related strain (R. alba KCTC 19413T) was 80.2 %, much lower than the species delineation threshold of 95-96 %. The genome of strain LNNU 22110T was 4.4 Mb, with a genomic DNA G+C content of 68.4 mol%. The diagnostic diamino acids in the peptidoglycan layer of strain LNNU 22110T were lysine, alanine, glycine, glutamic acid and aspartic acid. The predominant menaquinone was MK-8(H4). The major fatty acid (>10 %) was anteiso-C15 : 0. The polar lipid profile of strain LNNU 22110T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, diacylated phosphatidyl dimannoside, one unidentified glycolipid and two unidentified phospholipids. According to the phenotypic, phylogenetic and chemotaxonomic results, strain LNNU 22110T is considered to represent a novel species of the genus Ruania, for which the name Ruania rhizosphaerae sp. nov. is proposed. The type strain is LNNU 22110T (=KCTC 39807T=CGMCC 1.17105T).

Hoyosella suaedae sp. nov., a novel bacterium isolated from rhizosphere soil of Suaeda aralocaspica (Bunge) Freitag & Schütze.

A Gram-stain-positive, non-motile and coccus-shaped bacterium, designated strain LNNU 331112T, was isolated from the composite rhizosphere soil of the halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze, which was collected in Xinjiang, north-west China. Growth occurred at 10-45 °C, pH 6.0-11.0 and in the presence of 0-10 % NaCl (w/v). Phylogenetic analysis based on the 16S rRNA gene sequence suggested that strain LNNU 331112T belonged to the genus Hoyosella and showed 95.6, 95.5 and 95.4 % sequence similarities to Hoyosella altamirensis DSM 45258T, Hoyosella subflava CGMCC 4.3532T and Hoyosella rhizosphaerae CGMCC 1.15478T, respectively. The estimated digital DNA-DNA hybridization relatedness values between strain LNNU 331112T and the type strains of H. altamirensis DSM 45258T, H. subflava CGMCC 4.3532T and H. rhizosphaerae CGMCC 1.15478T were 18.9, 19.3 and 18.3 %, respectively. The average nucleotide identity values between strain LNNU 331112T and H. altamirensis DSM 45258T, H. subflava CGMCC 4.3532T and H. rhizosphaerae CGMCC 1.15478T were 72.6, 72.7 and 72.3 %, respectively. The genome sequence of strain LNNU 331112T showed 69.0-72.3 % average amino acid identity values in comparison with the related genome sequences of three validly published Hoyosella species. The genome of strain LNNU 331112T was 3.47 Mb, with a DNA G+C content of 68.4 mol%. A total of 3182 genes were identified as protein-coding in strain LNNU 331112T. Genomic analysis revealed that a number of genes involved in osmotic pressure regulation, intracellular pH homeostasis and potassium (K+) uptake protein were found in strain LNNU 331112T. The predominant menaquinones were MK-8 (44.6 %) and MK-7 (55.4 %), which differentiated strain LNNU 331112T from other three recognized Hoyosella species. Major fatty acids (>10 %) were C17 : 1 ω8c (33.8 %), C16 : 0 (23.3 %), C17 : 0 (12.8 %) and summed feature 3 (12.9 %), which also clearly separated strain LNNU 331112T from three recognized Hoyosella species. The polar lipid profile of strain LNNU 331112T included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, one unidentified glycolipid, one unidentified phospholipid and two unidentified lipids. According to the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 331112T is considered to represent a novel species of the genus Hoyosella, for which the name Hoyosella suaedae sp. nov. is proposed. The type strain is LNNU 331112T (=KCTC 39808T=CGMCC 1.17107T=DSM 103463T).

Full-length transcriptome analysis of Phytolacca americana and its congener P. icosandra and gene expression normalization in three Phytolaccaceae species.

BACKGROUND: Phytolaccaceae species in China are not only ornamental plants but also perennial herbs that are closely related to human health. However, both large-scale full-length cDNA sequencing and reference gene validation of Phytolaccaceae members are still lacking. Therefore, single-molecule real-time sequencing technology was employed to generate full-length transcriptome in invasive Phytolacca americana and non-invasive exotic P. icosandra. Based on the transcriptome data, RT-qPCR was employed to evaluate the gene expression stability in the two plant species and another indigenous congener P. acinosa. RESULTS: Total of 19.96 Gb and 19.75 Gb clean reads of P. americana and P. icosandra were generated, including 200,857 and 208,865 full length non-chimeric (FLNC) reads, respectively. Transcript clustering analysis of FLNC reads identified 89,082 and 98,448 consensus isoforms, including 86,989 and 96,764 high-quality ones. After removing redundant reads, 46,369 and 50,220 transcripts were obtained. Based on structure analysis, total 1675 and 1908 alternative splicing variants, 25,641 and 31,800 simple sequence repeats (SSR) as well as 34,971 and 36,841 complete coding sequences were detected separately. Furthermore, 3574 and 3833 lncRNA were predicted and 41,676 and 45,050 transcripts were annotated respectively. Subsequently, seven reference genes in the two plant species and a native species P. acinosa were selected and evaluated by RT-qPCR for gene expression analysis. When tested in different tissues (leaves, stems, roots and flowers), 18S rRNA showed the highest stability in P. americana, whether infested by Spodoptera litura or not. EF2 had the most stable expression in P. icosandra, while EF1-α was the most appropriate one when attacked by S. litura. EF1-α showed the highest stability in P.acinosa, whereas GAPDH was recommended when infested by S. litura. Moreover, EF1-α was the most stable one among the three plant species whenever germinating seeds or flowers only were considered. CONCLUSION: Full-length transcriptome of P. americana and P. icosandra were produced individually. Based on the transcriptome data, the expression stability of seven candidate reference genes under different experimental conditions was evaluated. These results would facilitate further exploration of functional and comparative genomic studies in Phytolaccaceae and provide insights into invasion success of P. americana.

Effect of Ag-1031 on apoptosis in gastric cancer AGS cells and its effects on the PI3K/AKT/mTOR signaling pathway.

PURPOSE: To investigate the effect of Ag-1031 on apoptosis of gastric cancer AGS cells and the PI3K/AKT/mTOR signaling pathway. METHODS: Gastric cancer cells were treated with different doses of Ag-1031. Cell viability was determined with MTT assay. Apoptosis was analyzed with Hoechst 33342 staining and Annexin V-FITC/PI double staining. The protein expression levels of p-PI3K, p-AKT, p-mTOR, PI3K, AKT and mTOR were assayed with western blotting method. RESULTS: Different doses of Ag-1031 significantly inhibited the proliferation of AGS cells. Moreover, Ag-1031 induced apoptosis,in gastric cancer cells. In addition, Ag-1031 significantly and dose-dependently inhibited the protein expressions of p-PI3K, p-AKT and p-mTOR. However, it had no effect on the protein expressions of PI3K, AKT and mTOR. CONCLUSION: In this study, it was found for the first time that Ag-1031 exerts an anti-tumor effect by induction apoptosis in gastric cancer AGS cells, through a mechanism related to inhibition of the activation of the PI3K/AKT/mTOR signaling pathway.

PLGA submicron particles containing chlorhexidine, calcium and phosphorus inhibit Enterococcus faecalis infection and improve the microhardness of dentin.

Enterococcus faecalis (E. faecalis), a Gram-positive facultative anaerobe, is reported to take responsibility for a large portion of refractory root canal infections and root canal re-infections of human teeth. Chlorhexidine is a strong bactericide against E. faecalis but cannot infiltrate into dentinal tubules. On the other hand, a common negative effect of root canal medicaments is the decrease of dentin microhardness. In this study, poly(D,L-lactic-co-glycolide) (PLGA) submicron particles were applied as delivery carriers to load and release the chlorhexidine as well as calcium and phosphorus. The release profiles, antibacterial ability against E. faecalis, infiltration ability into dentinal tubules, biocompatibility and effects on dentin microhardness of these particles were investigated. Results revealed that encapsulated chemicals could be released in a sustained manner from the particles. The particles also exhibited excellent biocompatibility on MC3T3-E1 cells and significant antimicrobial property against E. faecalis. On dentin slices, the particles could be driven into dentinal tubules by ultrasonic activiation and inhibit E. faecalis colonization. Besides, dentin slices medicated with the particles displayed an increase in microhardness. In conclusion, PLGA submicron particles carrying chlorhexidine, calcium and phosphorus could be developed into a new intra-canal disinfectant for dental treatments.

Identification and functional analysis of two P450 enzymes of Gossypium hirsutum involved in DMNT and TMTT biosynthesis.

The homoterpenes (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetraene (TMTT) are major herbivore-induced plant volatiles that can attract predatory or parasitic arthropods to protect injured plants from herbivore attack. In this study, DMNT and TMTT were confirmed to be emitted from cotton (Gossypium hirsutum) plants infested with chewing caterpillars or sucking bugs. Two CYP genes (GhCYP82L1 and GhCYP82L2) involved in homoterpene biosynthesis in G. hirsutum were newly identified and characterized. Yeast recombinant expression and enzyme assays indicated that the two GhCYP82Ls are both responsible for the conversion of (E)-nerolidol to DMNT and (E,E)-geranyllinalool to TMTT. The two heterologously expressed proteins without cytochrome P450 reductase fail to convert the substrates to homoterpenes. Quantitative real-time PCR (qPCR) analysis suggested that the two GhCYP82L genes were significantly up-regulated in leaves and stems of G. hirsutum after herbivore attack. Subsequently, electroantennogram recordings showed that electroantennal responses of Microplitis mediator and Peristenus spretus to DMNT and TMTT were both dose dependent. Laboratory behavioural bioassays showed that females of both wasp species responded positively to DMNT and males and females of M. mediator could be attracted by TMTT. The results provide a better understanding of homoterpene biosynthesis in G. hirsutum and of the potential influence of homoterpenes on the behaviour of natural enemies, which lay a foundation to study genetically modified homoterpene biosynthesis and its possible application in agricultural pest control.

The terpene synthase gene family in Gossypium hirsutum harbors a linalool synthase GhTPS12 implicated in direct defence responses against herbivores.

Herbivore-induced terpenes have been reported to function as ecological signals in plant-insect interactions. Here, we showed that insect-induced cotton volatile blends contained 16 terpenoid compounds with a relatively high level of linalool. The high diversity of terpene production is derived from a large terpene synthase (TPS) gene family. The TPS gene family of Gossypium hirsutum and Gossypium raimondii consist of 46 and 41 members, respectively. Twelve TPS genes (GhTPS4-15) could be isolated, and protein expression in Escherichia coli revealed catalytic activity for eight GhTPS. The upregulation of the majority of these eight genes additionally supports the function of these genes in herbivore-induced volatile biosynthesis. Furthermore, transgenic Nicotiana tabacum plants overexpressing GhTPS12 were generated, which produced relatively large amounts of (3S)-linalool. In choice tests, female adults of Helicoverpa armigera laid fewer eggs on transgenic plants compared with non-transformed controls. Meanwhile, Myzus persicae preferred feeding on wild-type leaves over leaves of transgenic plants. Our findings demonstrate that transcript accumulation of multiple TPS genes is mainly responsible for the production and diversity of herbivore-induced volatile terpenes in cotton. Also, these genes might play roles in plant defence, in particular, direct defence responses against herbivores.

Low Temperature Storage of Southern Rice Black-Streaked Dwarf Virus-Infected Rice Plants Cannot Sustain Virus Transmission by the Vector.

Southern rice black-streaked dwarf virus (SRBSDV) is a novel virus transmitted by white-backed planthopper Sogatella furcifera (Hováth) (Hemiptera: Delphacidae). Due to low virus transmission efficiency by the planthopper, researchers are frequently confronted with shortage of viruliferous vectors or infected rice plants, especially in winter and the following spring. To find new ways to maintain virus-infected materials, viral rice plants were stored at -80°C for 45 or 140 d and evaluated as virus sources in virus transmission by the vector. SRBSDV virions were not degraded during storage at -80°C as indicated by reverse transcription-polymerase chain reaction and reverse transcription real-time PCR detection. The planthopper nymphs fed on the infected thawed plants for 48 h survived at about 40% and showed positive detection of SRBSDV, but they lost the virus after feeding for another 20 d (the circulative transmission period) on noninfected plants. Transmission electron microscope images indicated broken capsid of virions in infected thawed leaves in contrast to integrity capsid of virions in infected fresh leaves. These results show that low temperature storage of SRBSDV-infected rice plants cannot sustain virus transmission by white-backed planthopper.

Interactive Effects of Southern Rice Black-Streaked Dwarf Virus Infection of Host Plant and Vector on Performance of the Vector, Sogatella furcifera (Homoptera: Delphacidae).

Performance of insect vectors can be influenced by the viruses they transmit, either directly by infection of the vectors or indirectly via infection of the host plants. Southern rice black-streaked dwarf virus (SRBSDV) is a propagative virus transmitted by the white-backed planthopper, Sogatella furcifera (Hovath). To elucidate the influence of SRBSDV on the performance of white-backed planthopper, life parameters of viruliferous and nonviruliferous white-backed planthopper fed rice seedlings infected or noninfected with SRBSDV were measured using a factorial design. Regardless of the infection status of the rice plant host, viruliferous white-backed planthopper nymphs took longer to develop from nymph to adult than did nonviruliferous nymphs. Viruliferous white-backed planthopper females deposited fewer eggs than nonviruliferous females and both viruliferous and nonviruliferous white-backed planthopper females laid fewer eggs on infected than on noninfected plants. Longevity of white-backed planthopper females was also affected by the infection status of the rice plant and white-backed planthopper. Nonviruliferous white-backed planthopper females that fed on infected rice plants lived longer than the other three treatment groups. These results indicate that the performance of white-backed planthopper is affected by SRBSDV either directly (by infection of white-backed planthopper) or indirectly (by infection of rice plant). The extended development of viruliferous nymphs and the prolonged life span of nonviruliferous adults on infected plants may increase their likelihood of transmitting virus, which would increase virus spread.

Revitalizing antitumor immunity: Leveraging nucleic acid sensors as therapeutic targets.

Nucleic acid sensors play a critical role in recognizing and responding to pathogenic nucleic acids as danger signals. Upon activation, these sensors initiate downstream signaling cascades that lead to the production and release of pro-inflammatory cytokines, chemokines, and type I interferons. These immune mediators orchestrate diverse effector responses, including the activation of immune cells and the modulation of the tumor microenvironment. However, careful consideration must be given to balancing the activation of nucleic acid sensors to avoid unwanted autoimmune or inflammatory responses. In this review, we provide an overview of nucleic acid sensors and their role in combating cancer through the perception of various aberrant nucleic acids and activation of the immune system. We discuss the connections between different programmed cell death modes and nucleic acid sensors. Finally, we outline the development of nucleic acid sensor agonists, highlighting how their potential as therapeutic targets opens up new avenues for cancer immunotherapy.

Rapid seedling emergence of invasive Phytolacca americana is related to higher soluble sugars produced by starch metabolism and photosynthesis compared to native P. acinosa.

Seedling emergence is an essential event in the life cycle of plants. Most invasive plants have an advantage in population colonization over native congeners. However, differential seedling emergence between invasive plants and native congeners, especially their mechanisms, have rarely been explored. In this study, we show that the seedlings of invasive Phytolacca americana emerge faster compared to native P. acinosa. Genome-wide transcriptomes of initially germinated seeds versus seedlings at 4 days after germination (DAG) suggested that differentially expressed genes (DEGs) in the photosynthesis-antenna proteins pathway were up-regulated in both P. americana and P. acinosa, while DEGs in starch and sucrose metabolism were significantly down-regulated in P. americana. Gene expression analysis indicated that photosynthesis-related DEGs reached their highest level at 3 DAG in P. americana, while they peaked at 4 DAG in P. acinosa. We also identified one ß-amylase gene in P. americana (PameAMYB) that showed the highest expression at 1 DAG, and two ß-amylase genes in P. acinosa that expressed lower than PameAMYB at 0 and 1 DAG. Enzymatic activity of ß-amylases also suggested that P. americana had the highest activity at 1 DAG, which was earlier than P. acinosa (at 4 DAG). Soluble sugars, the main source of energy for seedling emergence, were showed higher in P. americana than in P. acinosa, and reached the highest at 4 DAG that positively affected by photosynthesis. These results indicate that the rapid seedling emergence of invasive P. americana benefited from the high soluble sugar content produced by starch metabolism and photosynthesis. Altogether, this work contributes to our fundamental knowledge on physiological and molecular mechanisms for plant invasion success.

Engineering DMNT emission in cotton enhances direct and indirect defense against mirid bugs.

INTRODUCTION: As an important herbivore-induced plant volatile, (3E)-4,8-dimethyl-1,3,7-nonatriene (DMNT) is known for its defensive role against multiple insect pests, including attracting natural enemies. A terpene synthase (GhTPS14) and two cytochrome P450 (GhCYP82L1, GhCYP82L2) enzymes are involved in the de novo synthesis of DMNT in cotton. We conducted a study to test the potential of manipulating DMNT-synthesizing enzymes to enhance plant resistance to insects. OBJECTIVES: To manipulate DMNT emissions in cotton and generate cotton lines with increased resistance to mirid bug Apolygus lucorum. METHODS: Biosynthesis and emission of DMNT by cotton plants were altered using CRISPR/Cas9 and overexpression approaches. Dynamic headspace sampling and GC-MS analysis were used to collect, identify and quantify volatiles. The attractiveness and suitability of cotton lines against mirid bug and its parasitoid Peristenus spretus were evaluated through various assays. RESULTS: No DMNT emission was detected in knockout CAS-L1L2 line, where both GhCYP82L1 and GhCYP82L2 were knocked out. In contrast, gene-overexpressed lines released higher amounts of DMNT when infested by A. lucorum. At the flowering stage, L114 (co-overexpressing GhCYP82L1 and GhTPS14) emitted 10-15-fold higher amounts than controls. DMNT emission in overexpressed transgenic lines could be triggered by methyl jasmonate (MeJA) treatment. Apolygus lucorum and its parasitoid were far less attracted to the double edited CAS-L1L2 plants, however, co-overexpressed line L114 significantly attracted bugs and female wasps. A high dose of DMNT, comparable to the emission of L114, significantly inhibited the growth of A. lucorum, and further resulted in higher mortalities. CONCLUSION: Turning down DMNT emission attenuated the behavioral preferences of A. lucorum to cotton. Genetically modified cotton plants with elevated DMNT emission not only recruited parasitoids to enhance indirect defense, but also formed an ecological trap to kill the bugs. Therefore, manipulation of DMNT biosynthesis and emission in plants presents a promising strategy for controlling mirid bugs.

Prognostic Value of Hemoglobin Concentration on Renal Outcomes with Diabetic Kidney Disease: A Retrospective Cohort Study.

Objective: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated. Methods: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin. Results: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males. Conclusion: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.

Gut microbiome, T cell subsets, and cytokine analysis identify differential biomarkers in tuberculosis.

Introduction: The gut microbiota, T cell subsets, and cytokines participate in tuberculosis (TB) pathogenesis. To date, the mechanisms by which these factors interactively promote TB development at different time points remain largely unclear. In the context of this study, We looked into the microorganisms in the digestive tract, T cell types, and cytokines related to tuberculosis. Methods: According to QIIME2, we analyzed 16SrDNA sequencing of the gut microbiome on the Illumina MiSeq. Enzyme-linked immunosorbent assay was used to measure the concentrations of cytokines. Results: We showed the presence of 26 identifiable differential microbiomes in the gut and 44 metabolic pathways between healthy controls and the different time points in the development of TB in patients. Five bacterial genera (Bacteroides, Bifidobacterium, Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4/CD8, whereas three bacterial taxa (Faecalibacterium, Collinsella, and Clostridium) were most closely associated with CD4. Three bacterial taxa (Faecalibacterium, Ruminococcus, and Dorea) were most closely associated with IL-4. Ruminococcus was most closely associated with IL-2 and IL-10. Conclusion: Diverse microorganisms, subsets of T cells, and cytokines, exhibiting varying relative abundances and structural compositions, were observed in both healthy controls and patients throughout distinct phases of tuberculosis. Gaining insight into the function of the gut microbiome, T cell subsets, and cytokines may help modulate therapeutic strategies for TB.

Conformation of a Comb-like Chain in Solution: Effect of Backbone Rigidity.

We study the effect of backbone rigidity on the conformation of comb-like chains in dilute solution by using Brownian dynamics simulations. Our results demonstrate that the backbone rigidity can control the effect of side chains on the conformation of comb-like chains; that is, the relative strength of the excluded-volume interactions from backbone monomer-graft and graft-graft to backbone monomer-monomer gradually weakens with the increase of backbone rigidity. Only when the rigidity of the backbone tends to be flexible and the grafting density is high is the effect of excluded volume of graft-graft on the conformation of comb-like chains significant enough, and other cases can be ignored. Our results show that the radius of gyration of comb-like chains and the persistence length of the backbone are exponentially related to the stretching factor, where the power exponent exhibits an increase with the increase of the strength of bending energy. These finds provide new insights for characterizing the structure properties of comb-like chains.

Invasive Plants Have Higher Resistance to Native Generalist Herbivores Than Exotic Noninvasive Congeners.

Research on the invasive plant Phytolacca americana (L.) mostly focuses on its medicinal value and enrichment of heavy metals. However, little is known regarding its impact on native herbivorous insects. In this study, we explored the effects of P. americana and the exotic noninvasive Phytolacca icosandra (L.) on the Spodoptera litura (Fabricius) (native tobacco cutworm) via bioassay, oviposition preference, detoxifying enzyme activity analysis, and phytochemical determination. We found that the oviposition preference index (OPI) of S. litura feeding on P. icosandra was higher than that of P. americana. The developmental duration of S. litura feeding on P. icosandra was shorter than that of P. americana. Additionally, the Acetylcholinesterase (AchE) and Glutathione-S-transferase (GST) activities of S. litura feeding on P. americana were higher than that of S. litura feeding on artificial diets or P. icosandra. The content of lignin and flavonoids in P. americana was relatively high, whereas starch content was relatively low. These findings suggest invasive plants have higher resistance to herbivores, thereby suffering less damage than exotic noninvasive plants.

Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo.

Caries are chronic infections in which the cariogenic biofilm plays a critical role in disease occurrence and progression. Photodynamic therapy (PDT) is a new effective treatment that is receiving wide attention in the antibacterial field, but it can lead to the upregulation of heat shock proteins (HSPs), which enhances bacterial resistance. Herein, we incorporated HSP inhibitors with PDT to evaluate the effect on Streptococcus mutans, Streptococcus sobrinus, and Streptococcus sanguinis under planktonic conditions and on cariogenic biofilms. Additionally, a model of caries was established in 2-week-old rats, and anticaries properties were evaluated by Keyes' scoring. Importantly, the combination of HSP inhibitors and PDT had outstanding efficiency in inhibiting the growth of tested Streptococcus strains and the formation of either monomicrobial or multispecies biofilms in vitro. In addition, the quantity of colonized streptococci and the severity of carious lesions were also distinctly suppressed in vivo. Overall, the synergistic application of HSP inhibitors and PDT has promising potential in the prevention and treatment of dental caries. IMPORTANCE Effective therapies for the prevention and control of caries are urgently needed. Cariogenic streptococci play a key role in the occurrence and progression of caries. Recently, photodynamic therapy has been demonstrated to have good antibacterial efficiency, but it can cause a heat shock response in bacteria, which may weaken its practical effects. We indicate here an effective therapeutic strategy of combining heat shock protein inhibitors and photodynamic therapy, which shows excellent inhibition toward three dominant streptococci related to caries and suppression of carious progression in a rat model. Further development for clinical application is promising.