Fluorescence sensing of water in various organic solvents based on a novel cyclic polymer.

A sensor capable of sensing of water in various organic solvents ranging from water-soluble to water-miscible solvents is still a challenging task. In this research, a cyclic polymer fluorescence chemosensor (CPFC) has been developed for sensing of water by turn-on model in 9 organic solvents and turn-off model in DMA, where the broadest concentration range and the lowest detection limit was obtained for water in DMA (10 %-90 %) and dioxane (0.011 %), respectively. The sensing mechanism is explored by theory calculation and experimental investigation. The amphiphilic nature endows the polymer probe with great potential for measuring various contaminants from aqueous and nonaqueous mediums. Furthermore, the present search highlights the potential applications of cyclic polymer as fluorescence probes in the field of sensing.

Act1 drives chemoresistance via regulation of antioxidant RNA metabolism and redox homeostasis.

The IL-17 receptor adaptor molecule Act1, an RNA-binding protein, plays a critical role in IL-17-mediated cancer progression. Here, we report a novel mechanism of how IL-17/Act1 induces chemoresistance by modulating redox homeostasis through epitranscriptomic regulation of antioxidant RNA metabolism. Transcriptome-wide mapping of direct Act1-RNA interactions revealed that Act1 binds to the 5'UTR of antioxidant mRNAs and Wilms' tumor 1-associating protein (WTAP), a key regulator in m6A methyltransferase complex. Strikingly, Act1's binding sites are located in proximity to m6A modification sites, which allows Act1 to promote the recruitment of elF3G for cap-independent translation. Loss of Act1's RNA binding activity or Wtap knockdown abolished IL-17-induced m6A modification and translation of Wtap and antioxidant mRNAs, indicating a feedforward mechanism of the Act1-WTAP loop. We then developed antisense oligonucleotides (Wtap ASO) that specifically disrupt Act1's binding to Wtap mRNA, abolishing IL-17/Act1-WTAP-mediated antioxidant protein production during chemotherapy. Wtap ASO substantially increased the antitumor efficacy of cisplatin, demonstrating a potential therapeutic strategy for chemoresistance.

Development of a CT-assessed adiposity nomogram for predicting outcome in localized ccRCC.

PURPOSE: This study aimed to develop and validate a computed tomography-based nomogram assessing visceral and subcutaneous adiposity for predicting outcomes in localized clear cell renal cell carcinoma (ccRCC). METHODS: A cohort of 364 patients with pathologically confirmed ccRCC participated in this retrospective study, with 254 patients assigned to the training set and 110 to the validation set (a 7:3 distribution ratio). The adipose score (AS) was generated using the least absolute shrinkage and selection operator Cox regression. Subsequently, a nomogram was constructed by integrating the clinical independent predictor with the AS to predict disease-free survival (DFS) in localized ccRCC after surgery. The performance of the nomogram was compared with the University of California, Los Angeles, Integrated Staging System (UISS), and the Stage, Size, Grade, and Necrosis (SSIGN) score. RESULTS: In both the training and validation cohorts, the nomogram exhibited superior discrimination compared to SSIGN and UISS (C-index: 0.897 vs. 0.781 vs. 0.776 in the training cohort, and 0.752 vs. 0.596 vs. 0.686 in the validation cohort; 5 year AUC: 0.907 vs. 0.805 vs. 0.820 in the training cohort, and 0.832 vs. 0.577 vs. 0.726 in the validation cohort). Decision curve analysis (DCA) revealed a superior net benefit across a wider range of threshold probabilities for predicting 5 year DFS compared to UISS and SSIGN scores. CONCLUSIONS: The developed prognostic nomogram demonstrated high accuracy and overall superior performance compared to existing prognostic models.

Etiological Mechanisms and Genetic/Biological Modulation Related to PTH1R in Primary Failure of Tooth Eruption.

Primary failure of eruption (PFE) is a rare disorder that is characterized by the inability of a molar tooth/teeth to erupt to the occlusal plane or to normally react to orthodontic force. This condition is related to hereditary factors and has been extensively researched over many years. However, the etiological mechanisms of pathogenesis are still not fully understood. Evidence from studies on PFE cases has shown that PFE patients may carry parathyroid hormone 1 receptor (PTH1R) gene mutations, and genetic detection can be used to diagnose PFE at an early stage. PTH1R variants can lead to altered protein structure, impaired protein function, and abnormal biological activities of the cells, which may ultimately impact the behavior of teeth, as observed in PFE. Dental follicle cells play a critical role in tooth eruption and root development and are regulated by parathyroid hormone-related peptide (PTHrP)-PTH1R signaling in their differentiation and other activities. PTHrP-PTH1R signaling also regulates the activity of osteoblasts, osteoclasts and odontoclasts during tooth development and eruption. When interference occurs in the PTHrP-PTH1R signaling pathway, the normal function of dental follicles and bone remodeling are impaired. This review provides an overview of PTH1R variants and their correlation with PFE, and highlights that a disruption of PTHrP-PTH1R signaling impairs the normal process of tooth development and eruption, thus providing insight into the underlying mechanisms related to PTH1R and its role in driving PFE.

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

A TH17-intrinsic IL-1ß-STAT5 axis drives steroid resistance in autoimmune neuroinflammation.

Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (TH17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment. Interleukin-1ß (IL-1ß) induced a signal transducer and activator of transcription 5 (STAT5)-mediated steroid-resistant transcriptional program in TH17 cells, which promoted inflammatory cytokine production and suppressed Dex-induced anti-inflammatory genes. TH17-specific deletion of STAT5 ablated the IL-1ß-induced steroid-resistant transcriptional program and rendered EAE mice sensitive to Dex treatment. IL-1ß synergized with Dex to promote the STAT5-dependent expression of CD69 and the development of central nervous system (CNS)-resident CD69+ TH17 cells. Combined IL-1R blockade and Dex treatment ablated CNS-resident TH17 cells, reduced EAE severity, and prevented relapse. CD69+ tissue-resident TH17 cells were also detected in brain lesions of patients with multiple sclerosis. These findings (i) demonstrate that IL-1ß-STAT5 signaling in TH17 cells mediates steroid resistance and (ii) identify a therapeutic strategy for reversing steroid resistance in TH17-mediated CNS autoimmunity.

Leptin combined with withaferin A boost posthemorrhagic neurogenesis via activation of STAT3/SOCS3 pathway.

Neurogenesis as a potential strategy to improve the consequences of intracerebral hemorrhage (ICH). The current study investigates the effects of withaferin A (WFA) in combination with leptin (LEP) on ICH and neurogenesis mechanisms. LEP levels were dramatically reduced on days 7 and 14 following ICH insults in mice, but continuous WFA therapy significantly improved the potency of intrinsic LEP on day 14 after ICH. Furthermore, WFA combined with LEP enhances intrinsic neurogenesis and lessen motor deficits and long-term cognitive outcomes after ICH. In parallel, leptin deficiency in ob/ob mice limits enhancement of neurogenesis following ICH in response to WFA combined with LEP treatment. Importantly, the functional recovery conferred by WFA combined with LEP after ICH was inhibited by neurogenesis suppression. Mechanistically, this study unveiled that the signal transducer and activator of transcription-3 (STAT3) / suppressor of cytokine signaling-3 (SOCS3) pathway is a critical signaling pathway through which WFA combined with LEP treatment promotes intrinsic neurogenesis after ICH. Collectively, the results of this study elucidate the neuroprotective effects of WFA and LEP in ICH, and highlight a potential approach for ICH cell therapy.

Protocol for scarless genome editing of human pluripotent stem cell based on orthogonal selective reporters.

Human pluripotent stem cells (hPSCs) hold great promise for applications in regenerative medicine and disease modeling. Here, we present a protocol for establishing edited hPSC cell lines utilizing visualized orthogonal selective reporters. We describe steps for constructing plasmids, carrying out cell culture and electroporation, as well as performing drug-fluorescent dual enrichment, clone screening, and cell line characterization. This protocol facilitates the achievement of single-base homozygous mutations and reporter knockins, offering a reliable approach for precision genome editing.

The Combination of Buchloe dactyloides Engelm and Biochar Promotes the Remediation of Soil Contaminated with Polycyclic Aromatic Hydrocarbons.

Polycyclic aromatic hydrocarbons (PAHs) cause serious stress to biological health and the soil environment as persistent pollutants. Despite the wide use of biochar in promoting soil improvement, the mechanism of biochar removing soil PAHs through rhizosphere effect in the process of phytoremediation remain uncertain. In this study, the regulation of soil niche and microbial degradation strategies under plants and biochar were explored by analyzing the effects of plants and biochar on microbial community composition, soil metabolism and enzyme activity in the process of PAH degradation. The combination of plants and biochar significantly increased the removal of phenanthrene (6.10%), pyrene (11.50%), benzo[a]pyrene (106.02%) and PAHs (27.10%) when compared with natural attenuation, and significantly increased the removal of benzo[a]pyrene (34.51%) and PAHs (5.96%) when compared with phytoremediation. Compared with phytoremediation, the combination of plants and biochar significantly increased soil nutrient availability, enhanced soil enzyme activity (urease and catalase), improved soil microbial carbon metabolism and amino acid metabolism, thereby benefiting microbial resistance to PAH stress. In addition, the activity of soil enzymes (dehydrogenase, polyphenol oxidase and laccase) and the expression of genes involved in the degradation and microorganisms (streptomyces, curvularia, mortierella and acremonium) were up-regulated through the combined action of plants and biochar. In view of the aforementioned results, the combined application of plants and biochar can enhance the degradation of PAHs and alleviate the stress of PAH on soil microorganisms.

Can Gender-Specific Renal and Visceral Fat Be Evaluated by CT Predict Fuhrman Nuclear Classification of Clear Cell Renal Cell Carcinoma?

BACKGROUND: Evidence of the association between obesity and renal cell carcinoma progression is contradictory. The effects of renal cell carcinoma on fat distribution are still unknown. OBJECTIVE: The goal of this study was to determine the ability of various forms of fat deposition to predict the Fuhrman nuclear grade of clear cell renal cell carcinoma [ccRCC]. METHODS: This retrospective study included 320 patients with pathologically proven ccRCC [215 men and 105 women; 263 low-grade ccRCC and 57 highgrade ccRCC]. Based on computed tomography scans, adipose tissue in various body regions was classified into the perirenal fat area [PFA], visceral fat area [VFA], total fat area [TFA], subcutaneous fat area [SFA], and hepatic steatosis [HS]. Subsequently, the relative VFA [rVFA] was computed. Age, sex, body mass index, and maximal tumor diameter were also regarded as clinical factors. Univariate and multivariate logistic regression studies were conducted to evaluate whether there was an association between body fat composition and the Fuhrman classification and whether it was related to gender. RESULTS: After correcting for age, males with low-grade ccRCC exhibited higher TFA [257.6 vs. 203.0, p = 0.002], VFA [151.6 vs.115.5, p = 0.007], SFA [106.0 vs. 87.5, p = 0.015], PFA [55.1 vs. 30.4, p < 0.001], and HS [18% vs. 0%, p = 0.031] than those with high-grade ccRCC. There was no significant difference among rVFA in males. In females, there was no significant difference in any of the parameters. VFA and PFA remained independent predictors for high-grade ccRCC in males in both the monovariate [VFA: odds ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.997, p = 0.004; PFA: OR 0.949, 95% CI 0.930-0.970, p < 0.001] and multivariate [VFA: OR 1.028, 95% CI 1.001-1.074, p < 0.001; PFA: OR 0.878, 95% CI 0.833-0.926, p < 0.001] models. CONCLUSION: Gender-specific adipose tissue in different locations demonstrated varied values for predicting high-grade ccRCC and may be utilized as an independent predictor of high-grade ccRCC in male patients.

Posterior scleral reinforcement surgery effectively slows the rate of high myopic progression in children.

PURPOSE: To investigate the rate of axial length elongation and high myopia progression in operated eyes before and after posterior scleral reinforcement (PSR) surgery. METHODS: This was a retrospective study. Children with pathological myopia treated with PSR at Beijing Tongren Hospital between May 2013 and May 2020 were recruited into the PSR surgery group. Children matched for age and myopia were recruited into the control group. All children underwent comprehensive ophthalmologic examinations. The presurgical and postsurgical rates of axial length elongation and myopic (spherical equivalent) progression were calculated. RESULTS: A total of 35 PSR patients were included in the study. The mean age was 6.5±3.0 years (range 2 to 14 years). Mean follow-up was 544 days (range 216 to 1657 days). The rate of axial length elongation was significantly less after posterior scleral reinforcement surgery (0.505±0.048mm per year prior to surgery; 0.382±0.045mm per year after surgery, P<0.001). The rate of myopic progression decreased after posterior scleral reinforcement surgery (1.162±0.118 D per year prior to surgery; 0.153±0.437 D per year after surgery, P=0.0239). There was no statistically significant difference in axial length elongation or myopic progression between pre-inclusion and post-inclusion in the control group. Moreover, the children's best-corrected visual acuity was significantly improved after posterior scleral reinforcement surgery (P<0.001). CONCLUSION: Posterior scleral reinforcement surgery effectively decreased the rate of high myopic progression and axial length elongation in children.

Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.

Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.

The Genome of Bifidobacterium longum subsp. infantis YLGB-1496 Provides Insights into Its Carbohydrate Utilization and Genetic Stability.

Bifidobacterium longum subsp. infantis YLGB-1496 (YLGB-1496) is a probiotic strain isolated from human breast milk. The application of YLGB-1496 is influenced by carbohydrate utilization and genetic stability. This study used genome sequencing and morphology during continuous subculture to determine the carbohydrate utilization characteristics and genetic stability of YLGB-1496. The complete genome sequence of YLGB-1496 consists of 2,758,242 base pairs, 2442 coding sequences, and a GC content of 59.87%. A comparison of carbohydrate transport and metabolism genes of Bifidobacterium longum subsp. infantis (B. infantis) showed that YLGB-1496 was rich in glycosyl hydrolase 13, 20, 25, and 109 gene families. During continuous subculture, the growth characteristics and fermentation activity of the strain were highly stable. The bacterial cell surface and edges of the 1000th-generation strains were progressively smoother and well-defined, with no perforations or breaks in the cell wall. There were 20 SNP loci at the 1000th generation, fulfilling the requirement of belonging to the same strain. The presence of genes associated with cell adhesion and the absence of resistance genes supported the probiotic characteristics of the strain. The data obtained in this study provide insights into broad-spectrum carbohydrate utilization, genomic stability, and probiotic properties of YLGB-1496, which provide theoretical support to promote the use of YLGB-1496.

Biological Valorization of Lignin-Derived Aromatics in Hydrolysate to Protocatechuic Acid by Engineered Pseudomonas putida KT2440.

Alongside fermentable sugars, weak acids, and furan derivatives, lignocellulosic hydrolysates contain non-negligible amounts of lignin-derived aromatic compounds. The biological funnel of lignin offers a new strategy for the "natural" production of protocatechuic acid (PCA). Herein, Pseudomonas putida KT2440 was engineered to produce PCA from lignin-derived monomers in hydrolysates by knocking out protocatechuate 3,4-dioxygenase and overexpressing vanillate-O-demethylase endogenously, while acetic acid was used for cell growth. The sugar catabolism was further blocked to prevent the loss of fermentable sugar. Using the engineered strain, a total of 253.88 mg/L of PCA was obtained with a yield of 70.85% from corncob hydrolysate 1. The highest titer of 433.72 mg/L of PCA was achieved using corncob hydrolysate 2 without any additional nutrients. This study highlights the potential ability of engineered strains to address the challenges of PCA production from lignocellulosic hydrolysate, providing novel insights into the utilization of hydrolysates.

Uncovering key salt-tolerant regulators through a combined eQTL and GWAS analysis using the super pan-genome in rice.

For sessile plants, gene expression plays a pivotal role in responding to salinity stress by activating or suppressing specific genes. However, our knowledge of genetic variations governing gene expression in response to salt stress remains limited in natural germplasm. Through transcriptome analysis of the Global Mini-Core Rice Collection consisting of a panel of 202 accessions, we identified 22 345 and 27 610 expression quantitative trait loci associated with the expression of 7787 and 9361 eGenes under normal and salt-stress conditions, respectively, leveraging the super pan-genome map. Notably, combined with genome-wide association studies, we swiftly pinpointed the potential candidate gene STG5-a major salt-tolerant locus known as qSTS5. Intriguingly, STG5 is required for maintaining Na+/K+ homeostasis by directly regulating the transcription of multiple members of the OsHKT gene family. Our study sheds light on how genetic variants influence the dynamic changes in gene expression responding to salinity stress and provides a valuable resource for the mining of salt-tolerant genes in the future.

[Effect of different cleaning methods on bond strength and surface wettability of high translucency zirconia].

PURPOSE: To study the effect of different cleaning methods on the shear bond strength of self-adhesive resin cement to saliva-contaminated high translucency zirconia and surface wettability. METHODS: Eighty zirconia specimens were randomly divided into 5 groups (n=16), i.e., control group(not contaminated), 75% ethanol group,cleaning paste group,airborne-particle abrasion group, and atmospheric pressure cold plasma group. The contact angles was measured, shear bond strength were examined, and fracture types were determined. SPSS 26.0 software package was used for statistical analysis of the data. RESULTS: The atmospheric pressure cold plasma group produced the lowest contact angle(P＜0.05). The shear bond strength of the airborne-particle abrasion group, the cleaning paste group and the atmospheric pressure cold plasma group respectively were similar to the control group without significant difference(P＞0.05), while those were significantly higher than 75% ethanol group(P＜0.05). The mixed fracture mode of the atmospheric pressure cold plasma group evidently increased. CONCLUSIONS: Airborne-particle abrasion, cleaning paste and atmospheric pressure cold plasma overcome the effects of saliva contamination, producing the shear bond strength to zirconia similar to the control group. The atmospheric pressure cold plasma improves hydrophilicity of high translucency zirconia significantly.

Discovery of olimycin E from Streptomyces sp. 11695.

A new natural product olimycin E (1), together with two known compounds of divergolide R (2) and olimycin B (3), were obtained from the marine-derived Streptomyces sp. 11695. The structures of 1-3 were established on the basis of HRESIMS as well as 1D and 2D NMR datasets. The absolute configuration of 1 is identified as 4 R, 6S, 7S, 10 R by comparison the experiment ECD with that of the theoretical ECD. Antibacterial results showed that compound 2 have antibacterial activities against Staphylococcus aureus and MRSA with the MIC values of 32 µg/mL, respectively.

Density-dependent species interactions modulate alpine treeline shifts.

Species interactions such as facilitation and competition play a crucial role in driving species range shifts. However, density dependence as a key feature of these processes has received little attention in both empirical and modelling studies. Herein, we used a novel, individual-based treeline model informed by rich in situ observations to quantify the contribution of density-dependent species interactions to alpine treeline dynamics, an iconic biome boundary recognized as an indicator of global warming. We found that competition and facilitation dominate in dense versus sparse vegetation scenarios respectively. The optimal balance between these two effects was identified at an intermediate vegetation thickness where the treeline elevation was the highest. Furthermore, treeline shift rates decreased sharply with vegetation thickness and the associated transition from positive to negative species interactions. We thus postulate that vegetation density must be considered when modelling species range dynamics to avoid inadequate predictions of its responses to climate warming.