X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

The impact of combined administration of ropivacaine and dexamethasone on postoperative analgesia in perianal surgery with pudendal nerve block under ultrasound guidance: a prospective randomized controlled study.

Background: In recent years, severe pain after perianal surgery has seriously affected the prognosis of hospitalized patients. How to maximize the improvement of postoperative pain and perioperative comfort becomes particularly important. Methods: This study was a double-blind randomized controlled trial (Registration No.: ChiCTR2100048760, Registration Date: 16 July 2021, Link: www.chictr.org.cn/showproj.html?proj=130226), and patients were randomly divided into two groups: one group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine (P group), and the other group underwent postoperative 20 mL bilateral pudendal nerve block with 0.5% ropivacaine + 8 mg dexamethasone (PD group). The primary outcome was the incidence of moderate to severe pain at the first postoperative dressing change. Secondary outcomes included Quality of recovery-15 (QoR-15) score at 3 days after surgery, sleep quality, pain score at 3 days after surgery, and incidence of adverse events. Results: In the main outcome indicators, the incidence was 41.7% in the P group and 24.2% in the PD group (p = 0.01). The QoR-15 score and sleep quality in PD group were better than those in P group 2 days before surgery. The incidence of postoperative urinary retention was significantly decreased in PD group (p = 0.01). Conclusion: Local anesthesia with dexamethasone combined with pudendal nerve block after perianal surgery can reduce the incidence of moderate to severe pain during the first dressing change. This may be one of the approaches to multimodal analgesia after perianal surgery. Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2100048760.

[H3K27me3 Expression Level and Its Epigenetic Regulation Mechanisms in Th17 Cell Differentiation in Patients With Ankylosing Spondylitis]. / å¼ºç›´æ€§è„ŠæŸ±ç‚Žæ‚£è€ H3K27me3è¡¨è¾¾æ°´å¹³åŠå ¶è°ƒæŽ§Th17ç»†èƒžåˆ†åŒ–çš„è¡¨è§‚é—ä¼ æœºåˆ¶.

Objective: To investigate the roles of histone H3K27me3 methylation and its regulatory enzymes JMJD3 and EZH2 in the differentiation of Th17 cells in ankylosing spondylitis (AS), to unveil their potential involvement in the pathogenesis of AS, and to provide new strategies and targets for the clinical treatment of AS by analyzing the methylation state of H3K27me3 and its interactions with Th17-related factors. Methods: A total of 84 AS patients (42 active AS patiens and 42 patients in the stable phase of AS) were enrolled for the study, while 84 healthy volunteers were enrolled as the controls. Blood samples were collected. Peripheral blood mononuclear cells were isolated. ELISA assay was performed to examine Th17 cells and the relevant cytokines IL-21, IL-22, and IL-17. The mRNA expressions of RORc, JAK2, and STAT3 were analyzed by RT-PCR, the protein expressions of RORc, JAK2/STAT3 pathway protein, H3K27me3 and the relevant protease (EZH2 and JMJD3) were determined by Western blot. Correlation between H3K27me3, EZH2 and JMJD3 and the key signaling pathway molecules of Th cell differentiation was analyzed by Pearson correlation analysis. Results: The mRNA expressions of RORc, JAK2, and STAT3 were significantly higher in the active phase group than those in the stable phase group ( P<0.05). The relative grayscale values of H3K27me3 and EZH2 in the active phase group were lower than those of the stable phase group, which were lower than those of the control group, with the differences being statistically significant ( P<0.05). The relative grayscale values of JMJD3, RORc, JAK2, pJAK2, STAT3, and pSTAT3 proteins were significantly higher in the active phase group than those in the stable phase group, which were higher than those in the control group (all P<0.05). The proportion of Th17 and the expression level of inflammatory factors in the active period group were higher than those in the other two groups (P<0.05). H3K27me3 was negatively correlated with RORc, JAK2, STAT3, and IL-17, JMJD3 was positvely correlated with JAK2, STAT3, and IL-17, and EZH2 was negatively correlated with JAK2, STAT3, and IL-17 (all P<0.05). Conclusion: The low expression of H3K27me3 in AS is influenced by the gene loci JMJD3 and EZH2, which can regulate the differentiation of Th17 cells and thus play a role in the pathogenesis and progression of AS.

ISODISTROTLaMTeO6 (M = Ga3+ and Mn3+): the critical role of electronic configuration and cation ordering in crystal structures.

In this work, PbSb2O6-type oxides LaMTeO6 (M = Ga3+ and Mn3+) were synthesized and structurally characterized by Rietveld refinements against high-resolution X-ray powder diffraction data. The Ga3+/Te6+ partial ordering within the honeycomb-like two-dimensional [GaTeO6]3- anionic layer leads to the loss of the inversion center between Ga3+ and Te6+; however the inversion center on the 3̄-roto-inversion axis is preserved, thereby resulting in a 2-fold PbSb2O6-type superstructure by doubling the c-axis associated with a structural symmetry descending from the original P3̄1m to P3̄1c symmetry. In contrast, LaMnTeO6 (P21/c) adopts a monoclinically distorted 4-fold superstructure with lattice dimensions of a ≈ aH, b ≈ √3aH, c ≈ 2cH, where aH and cH represent the lattice parameters of trigonal PbSb2O6. The formation of this P21/c-superstructure is attributed to the combination of complete Mn3+/Te6+ ordering and the first-order Jahn-Teller distortion of Mn3+ with the electronic configuration of d4. Such a monoclinic distortion can effectively lift the Mn3+ spin moments arranged on the triangular sublattice, resulting in a sharp peak for antiferromagnetic transition, which is in stark contrast to subtle magnetic transitions for PbSb2O6-type tellurates AMn(VI)TeO6 (A = alkaline earth and Pb2+) and LnCrTeO6 (Ln = rare earth) with higher structural symmetry. Our findings highlight that the electronic configuration effects of M-cations play a critical role in controlling the structure symmetry of LaMTeO6, providing a strategy to fine-tune the crystal structures and physical properties.

Precision control and parameter optimization in screw extrusion 3D printing of polypropylene materials.

Fused Deposition Modeling (FDM), a widely-utilized additive manufacturing (AM) technology, has found significant favor among automotive manufacturers. Polypropylene (PP) compound is extensively employed in the production of automotive parts due to its superior mechanical properties and formability. However, aiming at the problem of poor dimensional accuracy of pure PP parts, the quality of products can be enhanced by optimizing the combination of processing parameters. In this paper, the dimensional accuracy of 3D-printed components made from pure PP material is investigated. Key influencing factors such as infill percentage, infill pattern, layer thickness, and extrusion temperature are considered. To gain a deeper understanding, fluid simulation is conducted, and mathematical models are established to correlate processing parameters with dimensional accuracy. Furthermore, the Taguchi's experiments are designed and the experimental data are subjected to rigorous Signal-to-Noise ratio and ANOVA analyses. Within the experimental range, the lower extrusion temperature, infill percentage and layer thickness yield the best dimensional accuracy. Considering the influence factors of X, Y and Z directions, the optimal processing parameters for PP prints using screw extrusion 3D printers are determined as follows: an extrusion temperature of 210 °C, an infill percentage of 40 %, a layer thickness of 0.3 mm, and a concentric circle infill pattern. This study provides reference value for the subsequent improvement of the dimensional accuracy of the printed parts.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

Elucidating the mechanisms of Buyang Huanwu Decoction in treating chronic cerebral ischemia: A combined approach using network pharmacology, molecular docking, and in vivo validation.

OBJECTIVE: This study aimed to explore the potential mechanisms of Buyang Huanwu Decoction (BHD) in regulating the AKT/TP53 pathway and reducing inflammatory responses for the treatment of chronic cerebral ischemia (CCI) using UHPLC-QE-MS combined with network pharmacology, molecular docking techniques, and animal experiment validation. METHODS: Targets of seven herbal components in BHD, such as Astragalus membranaceus, Paeoniae Rubra Radix, and Ligusticum chuanxiong, were identified through TCMSP and HERB databases. CCI-related targets were obtained from DisGeNET and Genecards, with an intersection analysis conducted to determine shared targets between the disease and the herbal components. Functional enrichment analysis of these intersecting targets was performed. Networks of gene ontology and pathway associations with these targets were constructed and visualized. A pharmacological network involving intersecting genes and active components was delineated. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape 3.9.1. The top five genes from the PPI network and their corresponding active components underwent molecular docking. Finally, the 2-vessel occlusion (2-VO) induced CCI rat model was treated with BHD, and the network pharmacology findings were validated using Western blot, RT-PCR, behavioral tests, laser speckle imaging, ELISA, HE staining, Nissl staining, LFB staining, and immunohistochemistry and immunofluorescence. RESULTS: After filtration and deduplication, 150 intersecting genes were obtained, with the top five active components by Degree value identified as Quercetin, Beta-Sitosterol, Oleic Acid, Kaempferol, and Succinic Acid. KEGG pathway enrichment analysis linked key target genes significantly with Lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. The PPI network highlighted ALB, IL-6, AKT1, TP53, and IL-1ß as key protein targets. Molecular docking results showed the strongest binding affinity between ALB and Beta-Sitosterol. Behavioral tests using the Morris water maze indicated that both medium and high doses of BHD could enhance spatial memory in 2-VO model rats, with high-dose BHD being more effective. Laser speckle results showed that BHD at medium and high doses could facilitate CBF recovery in CCI rats, demonstrating a dose-response relationship. HE staining indicated that all doses of BHD could reduce neuronal damage in the cortex and hippocampal CA1 region to varying extents, with the highest dose being the most efficacious. Nissl staining showed that nimodipine and medium and high doses of BHD could alleviate Nissl body damage. LFB staining indicated that nimodipine and medium and high doses of BHD could reduce the pathological damage to fiber bundles and myelin sheaths in the internal capsule and corpus callosum of CCI rats. ELISA results showed that nimodipine and BHD at medium and high doses could decrease the levels of TNF-α, IL-6, IL-17, and IL-1ß in the serum of CCI rats (p < 0.05). Immunohistochemistry and immunofluorescence demonstrated that BHD could activate the AKT signaling pathway and inhibit TP53 in treating CCI. Western blot and RT-PCR results indicated that nimodipine and all doses of BHD could upregulate Akt1 expression and downregulate Alb, Tp53, Il-1ß, and Il-6 expression in the hippocampus of CCI rats to varying degrees (p < 0.05). CONCLUSION: BHD exerts therapeutic effects in the treatment of CCI by regulating targets, such as AKT1, ALB, TP53, IL-1ß, and IL-6, and reducing inflammatory responses.

Extracellular vesicles meet mitochondria: Potential roles in regenerative medicine.

Extracellular vesicles (EVs), secreted by most cells, act as natural cell-derived carriers for delivering proteins, nucleic acids, and organelles between cells. Mitochondria are highly dynamic organelles responsible for energy production and cellular physiological processes. Recent evidence has highlighted the pivotal role of EVs in intercellular mitochondrial content transfer, including mitochondrial DNA (mtDNA), proteins, and intact mitochondria. Intriguingly, mitochondria are crucial mediators of EVs release, suggesting an interplay between EVs and mitochondria and their potential implications in physiology and pathology. However, in this expanding field, much remains unknown regarding the function and mechanism of crosstalk between EVs and mitochondria and the transport of mitochondrial EVs. Herein, we shed light on the physiological and pathological functions of EVs and mitochondria, potential mechanisms underlying their interactions, delivery of mitochondria-rich EVs, and their clinical applications in regenerative medicine.

Grain Protein Content Phenotyping in Rice via Hyperspectral Imaging Technology and a Genome-Wide Association Study.

Efficient and accurate acquisition of the rice grain protein content (GPC) is important for selecting high-quality rice varieties, and remote sensing technology is an attractive potential method for this task. However, the majority of multispectral sensors are poor predictors of GPC due to their broad spectral bands. Hyperspectral technology provides a new analytical technology for bridging the gap between phenomics and genomics. However, the small size of typical datasets is a constraint for model construction for estimating GPC, limiting their accuracy and reducing their ability to generalize to a wide range of varieties. In this study, we used hyperspectral data of rice grains from 515 japonica varieties and deep convolution generative adversarial networks (DCGANs) to generate simulated data to improve the model accuracy. Features sensitive to GPC were extracted after applying a continuous wavelet transform (CWT), and the estimated GPC model was constructed by partial least squares regression (PLSR). Finally, a genome-wide association study (GWAS) was applied to the measured and generated datasets to detect GPC loci. The results demonstrated that the simulated GPC values generated after 8,000 epochs were closest to the measured values. The wavelet feature (WF1743, 2), obtained from the data with the addition of 200 simulated samples, exhibited the highest GPC estimation accuracy (R 2 = 0.58 and RRMSE = 6.70%). The GWAS analysis showed that the estimated values based on the simulated data detected the same loci as the measured values, including the OsmtSSB1L gene related to grain storage protein. This study provides a new technique for the efficient genetic study of phenotypic traits in rice based on hyperspectral technology.

STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression.

Objective: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway. Methods: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model. Results: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH. Conclusion: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.

A novel framework for predicting glacial lake outburst debris flows in the Himalayas amidst climate change.

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

Model test study of bridge pile horizontal bearing behavior under landslide deformation.

Pile is a common foundation on the slope, which poses a serious threat to the construction and operation if the slope deformation and causes landslide. In this study, a model device of pile foundation on landslide was independently developed by relative displacement loading between pile and soil to explore the influence of landslide deformation on pile and analysis the soil failure rule and the deformation characteristics of pile in different stages of landslide deformation, a few model tests were completed including the relative displacement between soil and pile from 1 to 17 cm, and the pile diameter and the modulus of slide bed were also considered. The results indicated that: the evolution process of landslide deformation with pile foundation on could be divided into four stages including soil compaction, cracks growth, yield stage, and failure stage; ratios of the maximum soil pressure and bending moment growth from the soil compaction stage to the cracks growth stage to the total growth in these four stages are both exceeding 60%; the soil pressure increases with the increase of pile diameter and sliding bed modulus. Therefore, it is best to effectively monitor and control the landslide in the initial soil compression stage that in soil compaction stage and methods such as increasing pile foundations or reinforcing the sliding bed can be used for protection.

Formation of marine oil snow by soot particles generated from burning of oils.

This study aims to investigate the interactions between marine oil snow (MOS) formation and soot particles derived from two distinct oils: condensate and heavy oil. Experimental findings demonstrate that the properties of oil droplets and soot particles play a key role in MOS formation. Peak MOS formation is observed within the initial days for condensate, while for heavy oil, peak formation occurs at a later stage. Furthermore, the addition of oils and soot particles influences the final concentrations of polycyclic aromatic hydrocarbons (PAHs) in MOS. Remarkably, the ranking order of PAHs with different rings in various MOS samples remains consistent: 4- > 3- > 5- > 2- > 6-ring. Specific diagnostic ratios such as Phe/Ant, Ant/(Ant + Phe), BaA/(Chr + BaA), and LMW/HMW effectively differentiate petrogenic and pyrogenic sources of PAHs in MOS. And stable ratios like Flu/(Pyr + Flu), InP/(InP + BghiP), and BaF/BkF are identified for source analysis of soot MOS.

Revealing the mechanisms of blood-brain barrier in chronic neurodegenerative disease: an opportunity for therapeutic intervention.

The brain microenvironment is tightly regulated, and the blood-brain barrier (BBB) plays a pivotal role in maintaining the homeostasis of the central nervous system. It effectively safeguards brain tissue from harmful substances in peripheral blood. However, both acute pathological factors and age-related biodegradation have the potential to compromise the integrity of the BBB and are associated with chronic neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as Epilepsy (EP). This association arises due to infiltration of peripheral foreign bodies including microorganisms, immune-inflammatory mediators, and plasma proteins into the central nervous system when the BBB is compromised. Nevertheless, these partial and generalized understandings do not prompt a shift from passive to active treatment approaches. Therefore, it is imperative to acquire a comprehensive and in-depth understanding of the intricate molecular mechanisms underlying vascular disease alterations associated with the onset and progression of chronic neurodegenerative disorders, as well as the subsequent homeostatic changes triggered by BBB impairment. The present article aims to systematically summarize and review recent scientific work with a specific focus on elucidating the fundamental mechanisms underlying BBB damage in AD, PD, and EP as well as their consequential impact on disease progression. These findings not only offer guidance for optimizing the physiological function of the BBB, but also provide valuable insights for developing intervention strategies aimed at early restoration of BBB structural integrity, thereby laying a solid foundation for designing drug delivery strategies centered around the BBB.

Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

Objective: To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Methods: Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. Results: During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. Conclusion: The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Discovery of 5-(Piperidin-4-yl)-1,2,4-oxadiazole Derivatives as a New Class of Human Caseinolytic Protease P Agonists for the Treatment of Hepatocellular Carcinoma.

Chemical agonism of human caseinolytic protease P (HsClpP) is increasingly being recognized as a potential anticancer strategy due to its critical role in maintaining mitochondrial homeostasis. We unveil the discovery of 5-(piperidin-4-yl)-1,2,4-oxadiazole derivatives as a novel class of HsClpP agonists and demonstrate for the first time the application of HsClpP agonists in the treatment of hepatocellular carcinoma (HCC) (Pace, A.; Pierro, P. The new era of 1,2,4-oxadiazoles. Org. Biomol. Chem. 2009, 7 (21), 4337-4348). Compound SL44 exhibited potent HsClpP agonistic activity in the α-casein hydrolysis assay (EC50 = 1.30 µM) and inhibited the proliferation of HCCLM3 cells (IC50 = 3.1 µM, 21.4-fold higher than hit ADX-47273). Mechanistically, SL44 induces degradation of respiratory chain complex subunits and leads to apoptosis in HCC cells. In vivo results demonstrated that SL44 has potent tumor growth inhibitory activity and has a superior safety profile compared to the kinase inhibitor sorafenib. Overall, we developed a novel class of HsClpP agonists that can potentially be used for the treatment of HCC.

Identification and expression of the Di19 gene family in response to abiotic stress in common bean (Phaseolus vulgaris L.).

Drought-induced 19 (Di19) protein plays critical biological functions in response to adversity as well as in plant growth and development. Exploring the role and mechanism of Di19 in abiotic stress responses is of great significance for improving plant tolerance. In this study, six Di19 genes were identified in the common bean (Phaseolus vulgaris L.), which were mainly derived from segmental duplications. These genes share conserved exon/intron structures and were classified into three subfamilies based on their phylogenetic relationships. The composition and arrangement of conserved motifs were consistent with their phylogenetic relationships. Many hormone- and stress-responsive elements were distributed in the promoters region of PvDi19 genes. Variations in histidine residues in the Cys2/His2 (C2H2) zinc-finger domains resulted in an atypical tertiary structure of PvDi19-5. Gene expression analysis showed rapid induction of PvDi19-1 in roots by 10% PEG treatment, and PvDi19-2 in leaves by 20% PEG treatment, respectively. Most PvDi19s exhibited insensitivity to saline-alkali stress, except for PvDi19-6, which was notably induced during later stages of treatment. The most common bean Di19 genes were inhibited or not regulated by cadmium stress, but the expression of PvDi19-6 in roots was significantly upregulated when subjected to lower concentrations of cadmium (5 mmol). Moreover, Di19s exhibited greater sensitivity to severe cold stress (6°C). These findings enhance our understanding of the role of PvDi19s in common bean abiotic stress responses and provide a basis for future genetic enhancements in common bean stress tolerance.

Design, synthesis and biological evaluation of novel naphthoquinothiazole derivatives as potent antitumor agents through inhibiting STAT3.

The signal transducer and activator of transcription 3 (STAT3) has been established as a crucial drug target in the development of antitumor agents. In this study, a series of 21 derivatives of the STAT3 inhibitor napabucasin were designed and synthesized. Through preliminary screening against tumor cell lines, SZ6 emerged as the most potent compound with half maximal inhibitory concentration (IC50) values of 46.3 nM, 66.4 nM, and 53.8 nM against HCT116, HepG2, and Hela cells respectively. Furthermore, SZ6 effectively suppressed tumor invasion and migration in HCT116 cell assays by inducing S-phase arrest and apoptosis through inhibition of Protein Kinase B (PKB/AKT) activity and induction of reactive oxygen species (ROS). The mechanism underlying SZ6's action involves inhibition of STAT3 phosphorylation, which was confirmed by western blotting analysis. Additionally, surface plasmon resonance (SPR) and cellular thermal shift assay (CETSA) demonstrated direct binding between SZ6 and STAT3. Notably, in vivo studies revealed that SZ6 significantly inhibited tumor growth without any observed organ toxicity. Collectively, these findings identify SZ6 as a promising STAT3 inhibitor for colorectal cancer treatment.

Matching periodate peak absorbance by far UVC at 222 nm promotes the degradation of micropollutants and energy efficiency.

Periodate (PI)-based advanced oxidation processes have gained increasing interest. This study for the first time elevates the light-activation capacity of PI by using far UVC at 222 nm (UV222/PI) without extra chemical inputs. The effectiveness and the underlying mechanisms of UV222/PI for the remediation of micropollutants were studied by selecting atenolol (ATL) as a representative. PI possessed a high molar absorption coefficient of 9480-6120 M-1 cm-1 at 222 nm in the pH range of 5.0-9.0, and it was rapidly decomposed by UV222 with first-order rate constants of 0.0055 to 0.002 s-1. ATL and the six other organic compounds were effectively degraded by the UV222/PI process under different conditions with the fluence-based rate constants generally two to hundred times higher than by UVA photolysis. Hydroxyl radical and ozone were confirmed as the major contributors to ATL degradation, while direct photolysis also played a role at higher pH or lower PI dosages. Degradation pathways of ATL were proposed including hydroxylation, demethylation, and oxidation. The high energy efficiency of the UV222/PI process was also confirmed. This study provides a cost-effective and convenient approach to enhance PI light-response activity for the treatment of micropollutants.

Microsurgical resection of a samii type D jugular foramen schwannoma via the carotid triangle without removal of bony structure: how I do it.

BACKGROUND: Samii Type-D jugular foramen schwannomas (JFSs) are the most challenging for neurosurgeons because of anatomical complexity. Various neurosurgical approaches have been described to gain access to JF. METHODS: We present a female with incidental diagnosis of the Type-D JFS. Complete radical resection was achieved via the carotid triangle approach without any bony structure removal. And the patient was discharged asymptomatic and without new-developed neurological deficits. CONCLUSIONS: The carotid triangle is a secure and appropriate approach for some cases of selected Type-D JFSs. However, the specific indications of this approach should be further explored and investigated.