Colonic long-term retention and colonization of probiotics by double-layer chitosan/tannic acid coating and microsphere embedding for treatment of ulcerative colitis and radiation enteritis.

Oral probiotics can alleviate enteric inflammations but their rapid transit through the gut limits their retention and colonization in the colon. Here, a novel strategy integrating the bacterial double-layer coating and hydrogel microsphere embedding techniques was used to highly enhance the colonic retention and colonization efficiency of Lactobacillus rhamnosus GG (LGG). LGG was coated by the double layers of chitosan (CS) and tannic acid (TA), and then embedded in calcium alginate (CA) hydrogel microspheres to form LGG@CT@CA. The microspheres resisted gastric liquids, improving LGG safe transit through the stomach to reach the colon. LGG@CT was rapidly released in the colon due to the good swelling of hydrogel microspheres. More importantly, LGG exhibited long-term retention up to 7 days in the colon and colonized the deep site of the colonic mucosa. LGG@CT@CA had a high therapeutic efficiency of ulcer colitis with the long colon and the low intestinal permeability of colonic tissues. LGG@CT@CA also alleviated the small intestinal damage induced by irradiation and the survival rates were improved. The mechanisms included local ROS decrease, IL-10 increase, and ferroptosis reduction in the small intestine. The oral colon-targeted system holds promise for oral probiotic therapy by the long-term retention and colonization in the colon.

Plant growth-promoting microorganisms drive K strategists through deterministic processes to alleviate biological stress caused by Fusarium oxysporum.

Soybean root rot, caused by soil-borne pathogens such as Fusarium oxysporum, frequently occurs in Northeast China and leads to a decline in soil health and becoming a bottleneck for soybean yield in the region. To address this issue, applying beneficial microorganisms and altering soil microbial community structure have become effective strategies. In this study, the 90-day soybean pot experiment was conducted to explore the assembly process and life strategy selection of bacterial communities in the rhizosphere of healthy (inoculated with Funneliformis mosseae, F group and treated with Pseudomonas putida, P group) and diseased (inoculated with F. oxysporum, O group) soybean plants, as well as the recovery effect of beneficial microorganisms on soil-borne diseases (combined treatments OP and OF). Results indicated that in healthy soils (P and F), microbial community assembly process in the soybean rhizosphere was entirely governed by heterogeneous selection (HeS, 100 %). However, inoculated with P. putida (OP) was primarily driven by stochastic processes (HeS 40 %, dispersal limitation (DL) 60 %), and the F. mosseae treatment (OF) predominantly followed a deterministic process (HeS 89 %, DL 11 %) in diseased soils. Inoculation of plant growth-promoting microorganisms (PGPMs) in diseased soil drove the life strategy of the rhizosphere bacterial community from r- to K-strategy, evident from the lower rRNA operon (rrn) copy numbers (O 3.7, OP 2.1, OF 2.3), higher G+ to G- ratios (O 0.47, OP 0.58, OF 0.57), and a higher abundance of oligotrophs (O 50 %, OP 53 %, OF 54 %). In healthy (P and F) and diseased (O, OP, OF) rhizosphere soils, OTU820, OTU6142, and OTU8841 under the K-strategy, and OTU6032 and OTU6917 under the r-strategy, which served as keystone species, had a significant promoting relationship with plant biomass and defense capabilities ( p ＜0.05). Additionally, inoculation of PGPMs improved autotoxin degradation and positively correlated with bacterial life strategies in both healthy and diseased soils (P, F, OP and OF) ( p ＜0.05). These findings enhance our understanding of soil-microbe interactions and offer new insights and precise control measures for soybean disease management and soil environment remediation.

Evaluation of droplet deposition parameters based on the Genetic-Otsu algorithm.

Pesticide spraying is a cost-effective way to control crop pests and diseases. The effectiveness of this method relies on the deposition and distribution of the spray droplets within the targeted application area. There is a critical need for an accurate and stable detection algorithm to evaluate the liquid droplet deposition parameters on the water-sensitive paper (WSP) and reduce the impact of image noise. This study acquired 90 WSP samples with diverse coverage through field spraying experiments. The droplets on the WSP were subsequently isolated, and the coverage and density were computed, employing the fixed threshold method, the Otsu threshold method, and our Genetic-Otsu threshold method. Based on the benchmark of manually measured data, an error analysis was conducted on the accuracy of three methods, and a comprehensive evaluation was carried out. The relative error results indicate that the Genetic-Otsu method proposed in this research demonstrates superior performance in detecting droplet coverage and density. The relative errors of droplet density in the sparse, medium, and dense droplet groups are 2.7%, 1.5%, and 2.0%, respectively. The relative errors of droplet coverage are 1.5%, 0.88%, and 1.2%, respectively. These results demonstrate that the Genetic-Otsu algorithm outperforms the other two algorithms. The proposed algorithm effectively identifies small-sized droplets and accurately distinguishes the multiple independent contours of adjacent droplets even in dense droplet groups, demonstrating excellent performance. Overall, the Genetic-Otsu algorithm offered a reliable solution for detecting droplet deposition parameters on WSP, providing an efficient tool for evaluating droplet deposition parameters in UAV pesticide spraying applications.

The role of 5-HTergic neuron activation in the rapid antidepressant-like effects of hypidone hydrochloride (YL-0919) in mice.

Introduction: Major depressive disorder (MDD) is a common and disabling mental health condition; the currently available treatments for MDD are insufficient to meet clinical needs due to their limited efficacy and slow onset of action. Hypidone hydrochloride (YL-0919) is a sigma-1 receptor agonist and a novel fast-acting antidepressant that is currently under clinical development. Methods: To further understand the fast-acting antidepressant activity of YL-0919, this study focused on the role of 5-HTergic neurons in the dorsal raphe nucleus (DRN) in mice. Using fiber photometry to assess neural activity in vivo and two behavioral assays (tail suspension test and forced swimming test) to evaluate antidepressant-like activity. Results: It was found that 3 or 7 days of YL-0919 treatment significantly activated serotonin (5-HT) neurons in the DRN and had significant antidepressant-like effects on mouse behaviors. Chemogenetic inhibition of 5-HTergic neurons in the DRN significantly blocked the antidepressant-like effect of YL-0919. In addition, YL-0919 treatment significantly increased the 5-HT levels in the prefrontal cortex (PFC). These changes were drastically different from those of the selective serotonin reuptake inhibitor (SSRI) fluoxetine, which suggested that the antidepressant-like effects of the two compounds were mechanistically different. Conclusion: Together, these results reveal a novel role of 5-HTergic neurons in the DRN in mediating the fast-acting antidepressant-like effects of YL-0919, revealing that these neurons are potential novel targets for the development of fast-acting antidepressants for the clinical management of MDD.

Hypothalamic-hindbrain circuit for consumption-induced fear regulation.

To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.

Different polysaccharide-enhanced probiotic and polyphenol dual-functional factor co-encapsulated microcapsules demonstrate acute colitis alleviation efficacy and food fortification.

Probiotics and polyphenols have multiple bioactivities, and developing co-encapsulated microcapsules (CM) is a novel strategy to enhance their nutritional diversity. However, the development of CMs is challenged by complicated processing, single types, and unclear in vivo effects and applications. In this study, the co-microencapsulations of polyphenol and probiotic were constructed using pectin, alginate (WGCA@LK), and Fu brick tea polysaccharides (WGCF@LK), respectively, with chitosan-whey isolate proteins by layer-by-layer coacervation reaction, and their protective effects, in vivo effectiveness, and application potential were evaluated. WGCA@LK improved the encapsulation rate of polyphenols (42.41 %), and remained high viability of probiotics after passing through gastric acidic environment (8.79 ± 0.04 log CFU/g) and storage for 4 weeks (4.59 ± 0.06 log CFU/g). WGCF@LK exhibited the highest total antioxidant activity (19.40 ± 0.25 µmol/mL) and its prebiotic activity removed the restriction on probiotic growth. WGCA@LK showed strong in vitro colonic adhesion, but WGCF@LK promoted in vivo retention of probiotics at 48 h. WGCF@LK showed excellent anti-inflammatory effects and alleviated symptoms of acute colitis in mice. These findings provide unique insights into the fortification of probiotic-polyphenol CMs by different polysaccharides and the development of novel health foods with rich functional hierarchies and superior therapeutic effects.

The first case of multiple myeloma treated with ASCT followed by Anti-BCMA CAR-T cells using retrovirus vector: A case report.

Chimeric antigen receptor T (CAR-T)-cell therapy targeting B-cell maturation antigen (BCMA) is currently one of the promising treatment methods for relapsed/refractory multiple myeloma (MM). Herein, this study is a case report on a 41-year-old male patient with MM. Unfortunately, he still developed multidrug-resistant, refractory, and bone marrow suppression after receiving multiline high-intensity chemotherapy. After a detailed evaluation, the physician recommended autologous hematopoietic stem cell transplantation (ASCT) support, followed by sequential immunotherapy with autologous anti- BCMA CAR-T cells. The CAR-T product is a novel anti-BCMA CAR-T based on Retrovirus vectors (RV). It was worth noting that the patient achieved VGPR (very good partial remission) one month after infusion of anti-BCMA CAR-T cells. Recent tests have found that the M protein was no longer detectable and the patient has achieved CR (complete response). Although grade 3 cytokine release syndrome (CRS) appeared, the symptom was well controlled and immune effector cell-associated neurotoxicity syndrome (ICANS) did not occur. This was the first case report of RV prepared anti-BCMA CAR-T cells combined with ASCT for the treatment of MM patient in clinical practice, indicating that the RV-based anti-BCMA-CAR-T cells with ASCT have excellent therapeutic efficacy and high safety in triple-refractory MM patients.

Highly Efficient Synergistic Chemotherapy and Magnetic Resonance Imaging for Targeted Ovarian Cancer Therapy Using Hyaluronic Acid-Coated Coordination Polymer Nanoparticles.

The diagnosis and treatment of ovarian cancer (OC) are still a grand challenge, more than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Magnetic resonance imaging (MRI) has shown superior results to other examinations in preoperative assessment, while cisplatin-based chemotherapy is the first-line treatment for OC. However, few previous studies have brought together the two rapidly expanding fields. Here a technique is presented using cisplatin prodrug (Pt-COOH), Fe3+, and natural polyphenols (Gossypol) to construct the nanoparticles (HA@PFG NPs) that have a stable structure, controllable drug release behavior, and high drug loading capacity. The acidic pH values in tumor sites facilitate the release of Fe3+, Pt-COOH, and Gossypol from HA@PFG NPs. Pt-COOH with GSH consumption and cisplatin-based chemotherapy plus Gossypol with pro-apoptotic effects displays a synergistic effect for killing tumor cells. Furthermore, the release of Fe3+ at the tumor sites promotes ferroptosis and enables MRI imaging of OC. In the patient-derived tumor xenograft (PDX) model, HA@PFG NPs alleviate the tumor activity. RNA sequencing analysis reveals that HA@PFG NPs ameliorate OC symptoms mainly through IL-6 signal pathways. This work combines MRI imaging with cisplatin-based chemotherapy, which holds great promise for OC diagnosis and synergistic therapy.

Neglected errors in ligament reconstruction surgery may increase graft-tunnel mismatch: A biomechanical study.

Tunnel widening is a frequent problem following arthroscopic ligament reconstruction surgery that may primarily arise from a graft-tunnel mismatch caused by errors in surgical instruments and methods. The present study aimed to observe the influence of current surgical instruments and methods on graft-tunnel matching. We established an in vitro model using porcine Achilles tendons and tibias, and compared traditional surgical instruments (control group) with custom instruments (experimental group). Graft measurements, bone-tunnel creation, and measurements of the maximum pullout force of the graft from the bone tunnel were performed. Results indicated that the measuring gauge developed by our research group (capable of accurate measurement of graft diameters) may mitigate errors arising from graft-diameter measurement using traditional measuring cylinders. Therefore, errors caused by current surgical instruments and surgical methods led to an increase in graft-tunnel mismatches. The degree of mismatch was greater at the tibial end than at the femoral end.

[Species diversity of dark septate endophytes in tundra plants of Changbai Mountains, Northeast China]. / é•¿ç™½å±±è‹”åŽŸæ¤ç‰©æ·±è‰²æœ‰éš”å† ç”ŸçœŸèŒç‰©ç§å¤šæ ·æ€§.

We isolated the dark septate endophytic (DSE) fungi from roots of typical plant species in the tundra of Changbai Mountains Nature Reserve, including Rhododendron aureum, R. conferentiatum, Vaccinium uliginosum, and Dryas octopetala, and studied their colonization. We further investigated the DSE community composition and species diversity of the four tundra plant species by using morphological characteristics combined with rDNA ITS sequence analysis. The results showed that DSE formed a typical structure of "microsclerotia" in roots of the four plant species. A total of 69 strains of DSE fungi were isolated from the root samples, belonging to 10 genera, and 12 species. They were Phialocephala fortinii, Alternaria alternata, A. tenuissima, Epicocum nigrum, Canariomyces microsporus, Colletotrichum spaethianum, C. camelliae, Leptophoria sp., Cladosporium cladosporioides, Phoma sp., Cadophora sp., and Discosia italica, respectively. The DSE fungal species diversity was rich, and all these fungal species were firstly reported as DSE fungi in the alpine tundra belt of China. Among them, Phialocephala fortinii was the common and dominant species of all tundra plants. The Simpson, Pielou, and Shannon diversity indices of DSE fungi of the four plant species of tundra differed significantly. Our results showed that tundra plants have rich diversity of DSE fungi, and they can form a good symbiotic relationship, which enhance the adaptability of tundra plants to the harsh environment.

Assessing Drug Uptake and Response Differences in 2D and 3D Cellular Environments Using Stimulated Raman Scattering Microscopy.

The architecture of cell culture, two-dimensional (2D) versus three-dimensional (3D), significantly impacts various cellular factors, including cell-cell interactions, nutrient and oxygen gradients, metabolic activity, and gene expression profiles. This can result in different cellular responses during cancer drug treatment, with 3D-cultured cells often exhibiting higher resistance to chemotherapeutic drugs. While various genetic and proteomic analyses have been employed to investigate the underlying mechanisms of this increased resistance, complementary techniques that provide experimental evidence of spatial molecular profiling data are limited. Stimulated Raman scattering (SRS) microscopy has demonstrated its capability to measure both intracellular drug uptake and growth inhibition. In this work, we applied three-band (C-D, C-H, and fingerprint regions) SRS imaging to 2D and 3D cell cultures and performed a comparative analysis of drug uptake and response with the goal of understanding whether the difference in drug uptake explains the drug resistance in 3D culture compared to 2D. Our investigations revealed that despite similar intracellular drug levels in 2D and 3D A549 cells during lapatinib treatment, the growth of 3D spheroids was less impacted, supporting an enhanced drug tolerance in the 3D microenvironment. We further elucidated drug penetration patterns and the resulting heterogeneous cellular responses across different spheroid layers. Additionally, we investigated the role of the extracellular matrix in modulating drug delivery and cell response and discovered that limited drug penetration in 3D could also contribute to lower drug response. Our study provides valuable insights into the intricate mechanisms of increased drug resistance in 3D tumor models during cancer drug treatments.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Implementation of Rapid Nucleic Acid Amplification Based on the Super Large Thermoelectric Cooler Rapid Temperature Rise and Fall Heating Module.

In the rapid development of molecular biology, nucleic acid amplification detection technology has received more and more attention. The traditional polymerase chain reaction (PCR) instrument has poor refrigeration performance during its transition from a high temperature to a low temperature in the temperature cycle, resulting in a longer PCR amplification cycle. Peltier element equipped with both heating and cooling functions was used, while the robust adaptive fuzzy proportional integral derivative (PID) algorithm was also utilized as the fundamental temperature control mechanism. The heating and cooling functions were switched through the state machine mode, and the PCR temperature control module was designed to achieve rapid temperature change. Cycle temperature test results showed that the fuzzy PID control algorithm was used to accurately control the temperature and achieve rapid temperature rise and fall (average rising speed = 11 °C/s, average falling speed = 8 °C/s) while preventing temperature overcharging, maintaining temperature stability, and achieving ultra-fast PCR amplification processes (45 temperature cycle time < 19 min). The quantitative results show that different amounts of fluorescence signals can be observed according to the different concentrations of added viral particles, and an analytical detection limit (LoD) as low as 10 copies per µL can be achieved with no false positive in the negative control. The results show that the TEC amplification of nucleic acid has a high detection rate, sensitivity, and stability. This study intended to solve the problem where the existing thermal cycle temperature control technology finds it difficult to meet various new development requirements, such as the rapid, efficient, and miniaturization of PCR.

Characterization of PANoptosis-related genes with immunoregulatory features in osteoarthritis.

This study aimed to characterize PANoptosis-related genes with immunoregulatory features in osteoarthritis (OA) and investigate their potential diagnostic and therapeutic implications. Gene expression data from OA patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis and functional enrichment analysis were conducted to identify PANoptosis-related genes (PRGs) associated with OA pathogenesis. A diagnostic model was developed using LASSO regression, and the diagnostic value of key PRGs was evaluated using Receiver Operating Characteristic Curve (ROC) analysis. The infiltration of immune cells and potential small molecule agents were also examined. A total of 39 differentially expressed PANoptosis-related genes (DE-PRGs) were identified, with functional enrichment analysis revealing their involvement in inflammatory response regulation and immune modulation pathways. Seven key PRGs, including CDKN1A, EZH2, MEG3, NR4A1, PIK3R2, S100A8, and SYVN1, were selected for diagnostic model construction, demonstrating high predictive performance in both training and validation datasets. The correlation between key PRGs and immune cell infiltration was explored. Additionally, molecular docking analysis identified APHA-compound-8 as a potential therapeutic agent targeting key PRGs. This study identified and analyzed PRGs in OA, uncovering their roles in immune regulation. Seven key PRGs were used to construct a diagnostic model with high predictive performance. The identified PRGs' correlation with immune cell infiltration was elucidated, and APHA-compound-8 was highlighted as a potential therapeutic agent. These findings offer novel diagnostic markers and therapeutic targets for OA, warranting further in vivo validation and exploration of clinical applications.

Clinical practice guidelines of Chinese patent medicine in China: A critical review.

OBJECTIVES: To analyze the methodology, evidence, recommendations, quality, and implementation of traditional Chinese patent medicine (CPM) guidelines. METHODS: We retrieved clinical application guidelines of CPM published from 2019 to 2022. Independent screening and data extraction were performed by two evaluators. The basic information about the guidelines, including evidence and recommendations, were extracted and statistically analyzed. Quality and implementation were evaluated using the Implementation Evaluation Tool and Appraisal of Guidelines for Research & Evaluation (AGREE) II. RESULTS: In total, 29 guidelines were analyzed, including 262 recommendations and 2308 references. All the CPM guidelines followed the principle of "evidence as a core, consensus as a supplement, and experience as a reference" and the methods provided by WHO Handbook. An average of 89 references were cited in each guideline and 8 in each recommendation. Randomized controlled trials and systematic reviews constituted 89 % and 0.9 %, respectively, of all references. Low or very low-quality evidence characterized 74.5 % and weak recommendations characterized 83.6 %. Of all recommendations, 13.7 % were based on expert consensus, and 9.5 % of strong recommendations were based on low or very low-quality evidence. The AGREE II scores for each domain were: scope and purpose (79.63 %) and editorial independence (79.27 %), followed by clarity of presentation (72.59 %), stakeholder involvement (69.99 %), rigor of development (53.97 %) and applicability (5.11 %). The implementation quality of most guidelines was either high (44.8 %) or moderate (55.2 %). CONCLUSIONS: The results for CPM guidelines were impressive in terms of methodology, quality, and implementation. However, confidence in CPM recommendations was downgraded by low quality of evidence.

Protective effects of a probiotic-fermented germinated grain complex on neurotransmitters and sleep quality in sleep-deprived mice.

Objective: To explore the effects of probiotic fermentation products of germinated grains on cognitive and sleep improvement in mice with sleep deprivation induced by chlorophenylalanine (PCPA), and to provide theoretical and experimental basis for the development of natural products to alleviate insomnia. Methods: ELISA and high-performance liquid chromatography (HPLC) were used to determine the contents of γ-aminobutyric acid and L-theanine in fermentation products. Open Field Test was used to analyze the changes of emotional behavior between groups before and after intervention. ELISA was used to analyze the changes of hypothalamic serotonin, GABA, glutamate, and serum interleukin 6. 16S rRNA sequencing was used to analyze the changes of intestinal flora before and after the intervention of compound fermentation products. LC-MS/MS was used to analyze the changes of intestinal SCFAs before and after the intervention. Results: The content of GABA and L-theanine in 7 L fermentation products was 12.555 µmol/L (1.295 mg/L) and 0.471 mg/mL by ELISA. Compared with the PCPA-induced Model group, the sleep duration of the KEY group was statistically significant (p < 0.0001). Compared with the PCPA-induced Model group, the number of crossing the central lattice in the KEY group was significantly increased, and the number of grooming was significantly reduced (all p < 0.05), suggesting that the anxiety behavior of the mice was improved. In addition, this study found that the compound fermentation products could significantly increase the content of neurotransmitters such as 5-HT, GABA and Glu in the hypothalamus of mice, reduce the content of inflammatory factors such as IL-6, IL-1ß and TNF-α in serum, regulate the structure of intestinal flora and increase the content of short-chain fatty acids. Conclusion: Probiotic fermentation products of germinated grains can significantly improve sleep deprivation in PCPA mice, which may be related to regulating the levels of neurotransmitters and inflammatory factors, improving the structure of intestinal flora, and increasing the content of short-chain fatty acids. This study provides new candidates and research directions for the development of natural drugs to alleviate insomnia.

Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.

Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.

Evaluating the therapeutic effects of NiaoDuQing particles on chronic kidney disease based on real world study.

BACKGROUND: NiaoDuQing Particle is the first Chinese herbal medicine approved by the China Food and Drug Administration for the treatment of chronic kidney disease. It has been used in clinical practice in China for over twenty years. However, there is limited literature reporting on the long-term therapeutic effects of NiaoDuQing Particles on chronic kidney disease patients. OBJECTIVE: This research aimed to comprehensively assess the therapeutic effect of NiaoDuQing Particles (NDQP) on chronic kidney disease patients based on clinical data analysis. METHODS: This study was carried out on a total of 148 participants diagnosed with different types of chronic kidney disease. Demographics information, chronic kidney disease classification and chronic kidney disease diganostic indicators were collected and analyzed before and after NiaoDuQing Particles treatment for 3, 6, 9, 12 and 18 months respectively. RESULTS: In all 148 patients, mean eGFR value was increased after NiaoDuQing Particles treatment for up to 18 months, and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). Mean uric acid value was decreased after NiaoDuQing Particles treatment for up to 18 months, and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). Mean urea nitrogen value was decreased after NiaoDuQing Particles treatment for up to 18 months and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). While mean creatinine value was decreased after NiaoDuQing Particles treatment for up to 18 months and was statistically significant at month 6 (P< 0.05). CONCLUSIONS: NiaoDuQing Particles could maintain the stable state of chronic kidney disease patients for up to 18 months especially in improving diagnostic indicators like eGFR, uric acid and urea nitrogen.

The CDK9-SPT5 Axis in Control of Transcription Elongation by RNAPII.

The RNA polymerase II (RNAPII) transcription cycle is regulated at every stage by a network of cyclin-dependent protein kinases (CDKs) and protein phosphatases. Progression of RNAPII from initiation to termination is marked by changing patterns of phosphorylation on the highly repetitive carboxy-terminal domain (CTD) of RPB1, its largest subunit, suggesting the existence of a CTD code. In parallel, the conserved transcription elongation factor SPT5, large subunit of the DRB sensitivity-inducing factor (DSIF), undergoes spatiotemporally regulated changes in phosphorylation state that may be directly linked to the transitions between transcription-cycle phases. Here we review insights gained from recent structural, biochemical, and genetic analyses of human SPT5, which suggest that two of its phosphorylated regions perform distinct functions at different points in transcription. Phosphorylation within a flexible, RNA-binding linker promotes release from the promoter-proximal pause-frequently a rate-limiting step in gene expression-whereas modifications in a repetitive carboxy-terminal region are thought to favor processive elongation, and are removed just prior to termination. Phosphorylations in both motifs depend on CDK9, catalytic subunit of positive transcription elongation factor b (P-TEFb); their different timing of accumulation on chromatin and function during the transcription cycle might reflect their removal by different phosphatases, different kinetics of phosphorylation by CDK9, or both. Perturbations of SPT5 regulation have profound impacts on viability and development in model organisms through largely unknown mechanisms, while enzymes that modify SPT5 have emerged as potential therapeutic targets in cancer; elucidating a putative SPT5 code is therefore a high priority.

Current chemotherapy strategies for adults with IDH-wildtype glioblastoma.

Introduction: Glioblastoma, despite advancements in molecular evolution, remains incurable and has low survival rates. Currently, two of the most commonly used chemotherapy regimens are temozolomide and CCNU. This review aims to provide a comprehensive analysis of the current status of chemotherapy strategies for GBM. Methods: We reviewed the published literature describing the chemotherapy regimen differences in system treatment of GBM reported in the last ten years and summarised the available information that may reveal the latest changes in chemotherapy. Results: In patients with adequate functioning, temozolomide and radiation are the primary treatments for newly diagnosed GBM. We recommend postoperative radiation therapy with concurrent and adjuvant temozolomide for patients with MGMT-methylated GBM who are less than 70 years old. Combining temozolomide and lomustine with radiation therapy may be an option for younger, fit patients, but efficacy data is inconclusive. For patients with unknown MGMT methylation status, radiation therapy combined with temozolomide remains the standard of care. We recommend hypofractionated radiation and concurrent temozolomide treatment for elderly patients over 70 years old who have satisfactory performance and no significant underlying health conditions. We should tailor treatment choices to each patient's personal preferences, previous treatments, function, quality of life, and overall care objectives. Conclusion: Radiation therapy, along with temozolomide, is still the standard of care for most people with MGMT-unmethylated GBMs because there aren't any better options, and it's generally safe and well-tolerated. These patients have a lower overall survival rate and less benefit from temozolomide, but there are no better alternatives. Clinical trial participation is encouraged.