Salicylic acid inhibits rice endocytic protein trafficking mediated by OsPIN3t and clathrin to affect root growth.

Salicylic acid (SA) plays important roles in different aspects of plant development, including root growth, where auxin is also a major player by means of its asymmetric distribution. However, the mechanism underlying the effect of SA on the development of rice roots remains poorly understood. Here, we show that SA inhibits rice root growth by interfering with auxin transport associated with the OsPIN3t- and clathrin-mediated gene regulatory network (GRN). SA inhibits root growth as well as Brefeldin A-sensitive trafficking through a non-canonical SA signaling mechanism. Transcriptome analysis of rice seedlings treated with SA revealed that the OsPIN3t auxin transporter is at the center of a GRN involving the coat protein clathrin. The root growth and endocytic trafficking in both the pin3t and clathrin heavy chain mutants were SA insensitivity. SA inhibitory effect on the endocytosis of OsPIN3t was dependent on clathrin; however, the root growth and endocytic trafficking mediated by tyrphostin A23 (TyrA23) were independent of the pin3t mutant under SA treatment. These data reveal that SA affects rice root growth through the convergence of transcriptional and non-SA signaling mechanisms involving OsPIN3t-mediated auxin transport and clathrin-mediated trafficking as key components.

Immobilization of rough morphotype Mycolicibacterium neoaurum R for androstadienedione production.

OBJECTIVES: Enhance the androstadienedione (Androst-1,4-diene-3,17-dione, ADD) production of rough morphotype Mycolicibacterium neoaurum R by repeated-batch fermentation of immobilized cells. RESULTS: M. neoaurum R was a rough colony morphotype variant, obtained from the routine plating of smooth M. neoaurum strain CICC 21097. M. neoaurum R showed rougher cell surface and aggregated in broth. The ADD production of M. neoaurum R was notably lower than that of M. neoaurum CICC 21097 during the free cell fermentation, but the yield gap could be erased after proper cell immobilization. Subsequently, repeated-batch fermentation of immobilized M. neoaurum R was performed to shorten the production cycle and enhance the bio-production efficiency of ADD. Through the optimization of the immobilization carriers and the co-solvents for phytosterols, the ADD productivity of M. neoaurum R immobilized by semi-expanded perlite reached 0.075 g/L/h during the repeated-batch fermentation for 40 days. CONCLUSIONS: The ADD production of the rough-type M. neoaurum R was notably enhanced by the immobilization onto semi-expanded perlite. Moreover, the ADD batch yields of M. neoaurum R immobilized by semi-expanded perlite were maintained at high levels during the repeated-batch fermentation.

The applicability of the Second Revision of the International Staging System for patients with multiple myeloma receiving immunomodulatory drugs or proteasome inhibitor-based regimens as induction treatment: A real-world analysis.

The Second Revision of the International Staging System (R2-ISS) was recently introduced to improve risk stratification over that provided by the extensively applied standard revised International Staging System (R-ISS). In addition to the variables included in the R-ISS, the R2-ISS incorporates chromosome 1q gain/amplification and divides the patients into 4 groups with different survival outcomes, better stratifying patients within the R-ISS intermediate-risk. The new model was developed based on a great quantity of data from patients participating in uniform clinical trials and has not been validated in real-world clinical practice. Therefore, we retrospectively analyzed the prognostic value of the R2-ISS in 474 consecutive patients with multiple myeloma receiving immunomodulatory drugs or proteasome inhibitor-based regimens as their first-line treatment. According to the R2-ISS, 41 (8.6%), 76 (16%), 275 (58%), and 82 (17.3%) patients were identified as R2-ISS I, R2-ISS II, R2-ISS III, and R2-ISS IV, respectively. The median progression-free survival (PFS) was 48 (95% CI: 38-58), 35 (95% CI: 23-47), 24 (95% CI: 21-27), and 12 (95% CI: 7-17) months, and the estimated median overall survival (OS) was 110 (95% CI: 42-178), 88 (95% CI: 75-101), 50 (95% CI: 43-57), and 26 (95% CI: 19-33) months (p < 0.001) in the 4 groups, respectively. The R2-ISS could also classify groups with distinct survival among patients with renal impairment or classified as R-ISS II. Adjusted by age, sex, treatment approaches and transplantation status, the R2-ISS was an independent prognostic factor associated with OS with a hazard ratio of 7.055 (95% CI: 3.626-13.726) (p < 0.001) for R2-ISS IV versus R2-ISS I and 2.707 (95% CI: 1.436-5.103) (p = 0.002) for R2-ISS III versus R2-ISS I. In conclusion, our results suggest that the R2-ISS is a simple and robust risk stratification tool for patients with multiple myeloma treated with novel drugs and could be used in everyday clinical practice.

Evaluation of the Mayo Additive Staging System in patients with newly diagnosed multiple myeloma: A real-world analysis.

OBJECTIVES: Recently, the Mayo Clinic introduced a new staging system (the Mayo Additive Staging System [MASS]) for patients with newly diagnosed multiple myeloma (NDMM) based on the number of high-risk (HR) abnormalities, including HR IgH translocations, 1q gain/amplification, chromosome 17 abnormalities, International Staging System (ISS)-III, and elevated lactate dehydrogenase. Patients with 0, 1, or ≥2 HR abnormalities were defined as stage I, II, or III, respectively. We aimed to validate the real-world prognostic value of the MASS. METHODS: We retrospectively analyzed the cytogenetic and laboratory results of 544 patients with NDMM at a single center. RESULTS: Ninety (16.5%) patients had no HR factors (MASS I), 193 (35.5%) had 1 HR factor (MASS II), and 261 (48%) had ≥2 HR factors (MASS III). The median progression-free survival (PFS) and overall survival (OS) times were 48, 28, and 20 months and 137, 73, and 39 months in the three groups, respectively (p < .001). In the subgroup analysis, patients had different OS outcomes based on the MASS when grouped by age, renal function, or therapeutic regimens. The MASS identified patients with the worst outcomes among those rated revised ISS II. CONCLUSION: The MASS system is a reliable risk stratification tool for patients with NDMM in real-world clinical practice.

Association of preoperative electrocardiographic markers with sepsis in elderly patients after general surgery.

BACKGROUND: Electrocardiographic markers, as surrogates for sympathetic excitotoxicity, are widely predictive of cardiovascular adverse events, but whether these markers can predict postsurgical sepsis (SS) is unclear. METHODS: We retrospectively analyzed patients who underwent abdominal surgery from March 2013 to May 2023. We collected basic data, comorbidities, blood samples, echocardiology, electrocardiogram, and surgical data, as well as short-term outcome. The primary endpoints were postsurgical SS, in which logistic regression analyses can identify independent risk factors. The optimal cut-off value predictive postsurgical SS both P wave and PR interval were calculated in the receiver operating characteristic curve (ROC). RESULTS: A total of 1988 subjects were analyzed, and the incidence of postsurgical SS was 3.8%. The mean age at enrollment was 68.6 ± 7.1 years, and 53.2% of the participants were men. In the ROC analysis, the areas under the curve (AUC) for P wave and PR interval predictive postsurgical SS were 0.615 (95%CI, 0.548-0.683; p = 0.001) and 0.618 (95%CI, 0.554-0.682; p = 0.001), respectively. The P wave and PR interval predicted postoperative sepsis with optimal discrimination of 103 and 157 ms, with a sensitivity of 0.744 and 0.419, and a specificity of 0.427 and 0.760. P-wave less than 103 ms or PR interval less than 157 ms associated with a 2.06 or 2.33 fold increase occurred risk postsurgical SS. CONCLUSIONS: Shorter P-wave and PR intervals were both independently associated with postsurgical SS. These preoperative electrophysiological markers could have potential useful for early recognition of postoperative SS.

Atractylenolide III suppresses senescence-associated secretome via inhibiting cGAS/NF-κB pathway in hepatic stellate cells.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Induction of aHSCs senescence by inhibiting SASP may be a potential therapeutic model against hepatic fibrosis. To evaluate the role of atractylenolide III (ATR III) in the development of chemotherapeutic drug-induced SASPs in hepatic stellate cells. Etoposide-induced senescent HSC-LX2 model was established and treated with ATR III at different concentrations (20, 30 and 40 µM). We found that ATR III dose-dependently enhanced senescence in etoposide-induced LX2 cells. ATR III dose-dependently decreased the release and expression of SASP factors (interleukin [IL]-1α, IL-1ß, IL6 and IL-8) in senescent cells. ATR III regulated cyclic GMP-AMP synthase (cGAS)/nuclear factor κ (NF-κB) signalling to affect SASP expression in senescent cells. The addition of 2'3' cGAMP counteracted the effect of ATR III. The release of SASP factors in the conditioned medium from senescent cells could affect cell migration, proliferation and contraction through paracrine manner. Our results indicated ATR III could still enter senescence and prevent the production of SASP and its paracrine effects in senescent cells, an effect that may be related to the possible inhibition of cGAS/NF-κB signalling by ATR III. Our study proves that ATR III may be an effective potential drug against liver fibrosis by promoting aHSC senescence, which can provide a new choice for the future clinical treatment of liver fibrosis.

Mendelian randomization highlights the causal association of obesity with periodontal diseases.

AIM: The underlying mechanisms connecting obesity and periodontal diseases remain unclear. This study investigates the potential causal association of obesity with periodontal diseases using Mendelian randomization (MR). MATERIALS AND METHODS: Single-nucleotide polymorphisms of obesity traits including body mass index (BMI), waist circumference (WC), and WC adjusted for BMI (WCadjBMI) from large-scale genome-wide association studies were screened for instrumental variables. The single trait periodontitis and the combined trait comprising periodontitis and loose teeth were adopted as surrogates for periodontal diseases. Inverse-variance weighted (IVW), series of sensitivity analyses and multivariable MR were employed to determine the association of obesity with periodontal diseases. RESULTS: IVW results showed that per 1-SD increment in BMI (odds ratio, OR = 1.115; 95% confidence interval [CI] = 1.064-1.169; p < .001) and WC (OR = 1.117; 95% CI = 1.052-1.185; p < .001), but not WCadjBMI, were significantly associated with an increased risk of periodontitis/loose teeth. Moreover, the MR estimates were consistent across other MR sensitivity analyses and multivariable MR. However, a causal association of obesity with the single trait periodontitis was not identified. CONCLUSIONS: The presented evidence supports previous epidemiological findings by showing a potential causal association of genetic liability to obesity with periodontal diseases. The biological mechanisms underlying this association warrant further investigation.

Internal heating method of loop-mediated isothermal amplification for detection of HPV-6 DNA.

Loop-mediated isothermal amplification (LAMP) is a promising diagnostic tool for genetic amplification, which is known for its rapid process, simple operation, high amplification efficiency, and excellent sensitivity. However, most of the existing heating methods are external for completion of molecular amplification with possibility of contamination of specimens. The present research provided an internal heating method for LAMP using magnetic nanoparticles (MNPs), which is called nano-LAMP. Near-infrared light with an excitation wavelength of 808 nm was employed as the heating source; hydroxy naphthol blue (HNB) was used as an indicator to conduct methodological research. We demonstrate that the best temperature was controlled at a working power of 2 W and 4.8 µg/µL concentration of nanoparticles. The lowest limit for the detection of HPV by the nano-LAMP method is 102 copies/mL, which was confirmed by a gel electrophoresis assay. In the feasibility investigation of validated clinical samples, all 10 positive HPV-6 specimens amplified by nano-LAMP were consistent with conventional LAMP methods. Therefore, the nano-LAMP detection method using internal heating of MNPs may bring a new vision to the exploration of thermostatic detection in the future.

CircRNA circ_0005273 contributes to the cisplatin resistance of cervical cancer cells by sponging miR-133b.

Circular RNAs (circRNAs) have been found to play important roles in drug resistance of human neoplasms. The aim of this study was to explore the effect of circ_0005273 on cisplatin (DDP) resistance of cervical cancer (CC) cells and identify its underlying mechanism. The quantitative real-time polymerase chain reaction (qRT-PCR) was performed to analyse circ_0005273 and miR-133b expressions, and cell counting kit-8 (CCK-8), Hoechst 33258 staining and caspase-3 activity analysis were performed to evaluate cell proliferation and apoptosis. Luciferase reporter, RNA binding protein immunoprecipitation (RIP) and RNA pull down assays were applied to explore the interaction between circ_0005273 and miR-133b. Our research showed that circ_0005273 and miR-133b expressions were upregulated and downregulated in DDP-resistant CC cancer tissues and cell lines, respectively. Both of circ_0005273 and miR-133b levels were correlated with FIGO stage, DDP status and overall survival rates. Knockdown of circ_0005273 enhanced the sensitivity of DDP-resistant CC cells to DDP by inhibiting cell proliferation and promoting cell apoptosis. Furthermore, circ_0005273 acts as a competing endogenous RNA to modulate miR-133b expression. Downregulation of miR-133b partly reversed the DDP sensitivity of circ_0005273 knockdown in DDP-resistant CC cells. In summary, our study elucidated the role of circ_0005273/miR-133b axis in DDP resistance of CC cells, which might be a potential therapeutic target for DDP-resistant CC patients. Impact StatementWhat is already known on this subject? The detailed regulatory mechanisms underlying DDP chemoresistance are still unclear. Recently, literatures reported that circ_0005273 exerts a regulatory role in the tumorigenesis and progression of human cancers including thyroid carcinoma, pancreatic carcinoma, colorectal carcinoma and breast carcinoma.What do the results of this study add? Circ_0005273 contributes to the DDP resistance of CC cells via sponging miR-133b.What are the implications of these findings for clinical practice and/or further research? The results help to reverse DDP chemoresistance, and the circ_0005273/miR-133b axis might be a potential therapeutic target for DDP-resistant CC patients.

INDITTO2 transposon conveys auxin-mediated DRO1 transcription for rice drought avoidance.

Transposable elements exist widely throughout plant genomes and play important roles in plant evolution. Auxin is an important regulator that is traditionally associated with root development and drought stress adaptation. The DEEPER ROOTING 1 (DRO1) gene is a key component of rice drought avoidance. Here, we identified a transposon that acts as an autonomous auxin-responsive promoter and its presence at specific genome positions conveys physiological adaptations related to drought avoidance. Rice varieties with a high and auxin-mediated transcription of DRO1 in the root tip show deeper and longer root phenotypes and are thus better adapted to drought. The INDITTO2 transposon contains an auxin response element and displays auxin-responsive promoter activity; it is thus able to convey auxin regulation of transcription to genes in its proximity. In the rice Acuce, which displays DRO1-mediated drought adaptation, the INDITTO2 transposon was found to be inserted at the promoter region of the DRO1 locus. Transgenesis-based insertion of the INDITTO2 transposon into the DRO1 promoter of the non-adapted rice variety Nipponbare was sufficient to promote its drought avoidance. Our data identify an example of how transposons can act as promoters and convey hormonal regulation to nearby loci, improving plant fitness in response to different abiotic stresses.