A novel minimally invasive endoscopic approach of thyroid surgery-endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach.

Background: Since the endoscopic thyroidectomy was firstly reported by Hüscher in 1997, there has been an ongoing debate regarding whether mainstream endoscopic thyroidectomy can be classified as minimally invasive surgery. In this study, we innovatively proposed the endoscopic thyroidectomy via sternocleidomastoid muscle posteroinferior approach (ETSPIA), a novel minimally invasive surgical technique, and compared its efficacy with the well-established transoral endoscopic thyroidectomy vestibular approach (TOETVA). Methods: We retrospectively analyzed 50 patients who underwent ETSPIA and 50 patients who underwent TOETVA at Beijing Tongren Hospital, comparing their clinical characteristics, operative duration, blood loss, postoperative alterations in parathyroid hormone (PTH) and serum calcium, recovery post-surgery, complications, and follow-up data. Results: The ETSPIA group had a shorter operation time compared to the TOETVA group (243.40±58.67 vs. 278.08±78.50 min; P=0.01). The ETSPIA group also had less intraoperative blood loss than the TOETVA group (20.60±10.58 vs. 33.00±11.11 mL; P<0.001). More central lymph nodes were dissected in the ETSPIA group compared to the TOETVA group (5.90±4.72 vs. 3.36±2.80; P=0.002). However, the difference in the number of positive central lymph nodes dissected was not statistically significant (1.38±2.33 for ETSPIA vs. 0.94±1.39 for TOETVA; P=0.26). The ETSPIA group had a shorter length of stay (LOS) compared to the TOETVA group (6.82±2.02 vs. 8.26±2.72 days; P=0.003). The alteration in PTH levels 1 day after surgery was less pronounced in the ETSPIA group compared to the TOETVA group (-26.38%±18.43% vs. -35.75%±22.95%; P=0.04). At the 1-month postoperative mark, the ETSPIA group showed a marginal increase in PTH levels, whereas the TOETVA group exhibited a slight decrease (10.12%±35.43% vs. -11.53%±29.51%; P=0.03). Regarding the average percentage change in serum calcium level 1 day after surgery, the ETSPIA group showed a smaller change, though this difference was not statistically significant (-4.79%±5.47% vs. -5.66%±3.90%; P=0.40). Furthermore, the incidence of hoarseness attributable to transient recurrent laryngeal nerve (RLN) injury in postoperative patients was lower in the ETSPIA group compared to the TOETVA group, but this difference did not reach statistical significance (0% vs. 4%; P=0.15). Conclusions: Overall, compared to TOETVA, the ETSPIA is characterized by a shorter operative route, enhanced protection of the parathyroid glands, reduced trauma, and expedited postoperative recovery.

Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren's syndrome.

SjÓ§gren's syndrome is a systemic autoimmune disease primarily targeting the salivary and lacrimal glands. Our previous investigations have shown that administration of interleukin-22 (IL-22), an IL-10 family cytokine known for its complex and context-dependent effects on tissues, either protective- or detrimental, to salivary glands leads to hypofunction and pathological changes of salivary glands in C57BL/6 mice and in non-obese diabetic (NOD) mice, the latter being a commonly used model of SjÓ§gren's syndrome. This study aims to delineate the pathophysiological roles of endogenously produced IL-22 in the development of salivary gland pathologies and dysfunction associated with SjÓ§gren's disease in the NOD mouse model. Our results reveal that neutralizing IL-22 offered a protective effect on salivary gland function without significantly affecting the immune cell infiltration of salivary glands or the autoantibody production. Blockade of IL-22 reduced the levels of phosphorylated STAT3 in salivary gland tissues of NOD mice, while its administration to salivary glands had the opposite effect. Correspondingly, the detrimental impact of exogenously applied IL-22 on salivary glands was almost completely abrogated by a specific STAT3 inhibitor. Moreover, IL-22 blockade led to a downregulation of protein amounts of Ten-Eleven-Translocation 2, a methylcytosine dioxygenase critical for mediating interferon-induced responses, in salivary gland epithelial cells. IL-22 neutralization also exerted a protective effect on the salivary gland epithelial cells that express high levels of surface EpCAM and bear the stem cell potential, and IL-22 treatment in vitro hampered the survival/expansion of these salivary gland stem cells, indicating a direct negative impact of IL-22 on these cells. In summary, this study has uncovered a critical pathogenic role of the endogenous IL-22 in the pathogenesis of Sjögren's disease-characteristic salivary gland dysfunction and provided initial evidence that this effect is dependent on STAT3 activation and potentially achieved through fostering Tet2-mediated interferon responses in salivary gland epithelial cells and negatively affecting the EpCAMhigh salivary gland stem cells.

Epigenetic silencing of KCTD8 promotes hepatocellular carcinoma growth by activating PI3K/AKT signaling.

Aim: The aim of current study is to explore the epigenetic changes and function of KCTD8 in human hepatocellular carcinoma (HCC). Materials & methods: HCC cell lines and tissue samples were employed. Methylation specific PCR, flow cytometry, immunoprecipitation and xenograft mouse models were used. Results: KCTD8 was methylated in 44.83% (104/232) of HCC and its methylation may act as an independent poor prognostic marker. KCTD8 expression was regulated by DNA methylation. KCTD8 suppressed HCC cell growth both in vitro and in vivo via inhibiting PI3K/AKT pathway. Conclusion: Methylation of KCTD8 is an independent poor prognostic marker, and epigenetic silencing of KCTD8 increases the malignant tendency in HCC.

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Ilexgenin A inhibits lipid accumulation in macrophages and reduces the progression of atherosclerosis through PTPN2/ERK1/2/ABCA1 signalling pathway.

Macrophage lipid accumulation indicates a pathological change in atherosclerosis. Ilexgenin A (IA), a pentacyclic triterpenoid compound, plays a role in preventing inflammation, bacterial infection, and fatty liver and induces a potential anti-atherogenic effect. However, the anti-atherosclerotic mechanism remains unclear. The present study investigated the effects of IA on lipid accumulation in macrophage-derived foam cells and atherogenesis in apoE-/- mice. Our results indicated that the expression of adenosine triphosphate-binding cassette transporter A1 (ABCA1) was up-regulated by IA, promoting cholesterol efflux and reducing lipid accumulation in macrophages, which may be regulated by the protein tyrosine phosphatase non-receptor type 2 (PTPN2)/ERK1/2 signalling pathway. IA attenuated the progression of atherosclerosis in high-fat diet-fed apoE-/- mice. PTPN2 knockdown with siRNA or treatment with an ERK1/2 agonist (Ro 67-7476) impeded the effects of IA on ABCA1 upregulation and cholesterol efflux in macrophages. These results suggest that IA inhibits macrophage lipid accumulation and alleviates atherosclerosis progression via the PTPN2/ERK1/2 signalling pathway.

PIM1/NF-κB/CCL2 blockade enhances anti-PD-1 therapy response by modulating macrophage infiltration and polarization in tumor microenvironment of NSCLC.

Elevated infiltration of tumor-associated macrophages (TAMs) drives tumor progression and correlates with poor prognosis for various tumor types. Our research identifies that the ablation of the Pim-1 proto-oncogene (PIM1) in non-small cell lung cancer (NSCLC) suppresses TAM infiltration and prevents them from polarizing toward the M2 phenotype, thereby reshaping the tumor immune microenvironment (TME). The predominant mechanism through which PIM1 exerts its impact on macrophage chemotaxis and polarization involves CC motif chemokine ligand 2 (CCL2). The expression level of PIM1 is positively correlated with high CCL2 expression in NSCLC, conferring a worse overall patient survival. Mechanistically, PIM1 deficiency facilitates the reprogramming of TAMs by targeting nuclear factor kappa beta (NF-κB) signaling and inhibits CCL2 transactivation by NSCLC cells. The decreased secretion of CCL2 impedes TAM accumulation and their polarization toward a pro-tumoral phenotype. Furthermore, Dual blockade of Pim1 and PD-1 collaboratively suppressed tumor growth, repolarized macrophages, and boosted the efficacy of anti-PD-1 antibody. Collectively, our findings elucidate the pivotal role of PIM1 in orchestrating TAMs within the TME of NSCLC and highlight the potential of PIM1 inhibition as a strategy for enhancing the efficacy of cancer immunotherapy.

Celiac trunk aortic dissection induced by bevacizumab therapy for rectal cancer: A case report.

RATIONALE: Bevacizumab (Bev) is a humanized monoclonal antibody that targets vascular endothelial growth factor A and is primarily used for the treatment of various solid tumors. Aortic dissection (AD) is a severe vascular disease caused by the tearing of the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of different layers of the aortic wall. However, the pathogenesis is not fully understood. Some studies have suggested that Bev treatment is associated with the occurrence of AD. PATIENT CONCERNS: A 67-year-old Chinese male was diagnosed with rectal cancer accompanied by liver and lung metastasis. Three days after starting combined chemotherapy with Bev, the patient developed persistent abdominal pain. Abdominal CT scan revealed celiac trunk AD in the abdominal aorta. DIAGNOSES: The patient was diagnosed with rectal cancer accompanied by liver and lung metastases. Abdominal CT tomography revealed a celiac trunk AD. INTERVENTIONS: Somatostatin combined with valsartan was used to control blood pressure. The patient was subsequently referred for vascular surgery and underwent an abdominal aortic angiography. Conservative treatment was continued. OUTCOMES: Three months after the initiation of treatment, follow-up abdominal CT scans showed stability in the condition of celiac trunk AD, with no abdominal pain or hypertension. There were no signs of worsening dissection, aneurysm formation, or inadequate perfusion of end organs. LESSONS: There may be a connection between Bev and elevated blood pressure as well as celiac trunk AD.

Tibetan Plateau Runoff and Evapotranspiration Dataset by an observation-constrained cryosphere-hydrology model.

Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998-2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED's monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944-0.995), Bias (-0.68-0.53), and Root Mean Square Error (5.50-15.59 mm). Additionally, TPRED's monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED's annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

Unveiling the impact of glutathione (GSH) and p53 gene deletion on tumor cell metabolism by amino acid and proteomics analysis.

Background: Tumor cell inhibition is a pivotal focus in anti-cancer research, and extensive investigations have been conducted regarding the role of p53. Numerous studies have highlighted its close association with reactive oxygen species (ROS). However, the precise impact of the antioxidant glutathione (GSH) in this context remains inadequately elucidated. Here, we will elucidate the anti-cancer mechanisms mediated by p53 following treatment with GSH. Methods: In this study, we employed a p53 gene knockout approach in SW480 colorectal cells and conducted comprehensive analyses of 20 amino acids and proteomics using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Results: These analyses unveiled profound alterations in amino acids and proteins triggered by GSH treatment, shedding light on novel phenomena and delineating the intricate interplay between GSH and cellular proteins. The deletion of the p53 gene exerts a profound influence on tumor cell proliferation. Moreover, tumor cell proliferation is significantly affected by elevated GSH levels. Importantly, in the absence of the p53 gene, cells exhibit heightened sensitivity to GSH, leading to inhibited cell growth. The combined therapeutic approach involving GSH and p53 gene deletion expedites the demise of tumor cells. It is noteworthy that this treatment leads to a marked decline in amino acid metabolism, particularly affecting the down-regulation of methionine (Met) and phenylalanine (Phe) amino acids. Among the 41 proteins displaying significant changes, 8 exhibit consistent alterations, with 5 experiencing decreased levels and 3 demonstrating increased quantities. These proteins primarily participate in crucial cellular metabolic processes and immune functions. Conclusions: In conclusion, the concurrent administration of GSH treatment and p53 gene deletion triggers substantial modifications in the amino acid and protein metabolism of tumor cells, primarily characterized by down-regulation. This, in turn, compromises cell metabolic activity and immune function, ultimately culminating in the demise of tumor cells. These newfound insights hold promising implications and could pave the way for the development of straightforward and efficacious anti-cancer treatments.

Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Non-Invasive Monitoring of the Impact of Low-Level Viremia on Liver Fibrosis in Treated Chronic Hepatitis B Patients.

Background: Chronic hepatitis B (CHB) presents a global health challenge due to its potential to cause severe liver conditions such as hepatocellular carcinoma (HCC) and cirrhosis. Prior research has established a correlation between CHB infection with low-level viremia (LLV) and liver disease progression, such as increased HCC incidence. This study aims to investigate whether LLV during treatment with nucleos(t)ide analogs (NAs) contributes to the accelerated progression of liver fibrosis (LF). Methods: This retrospective cohort study at Jinhua Central Hospital focused on CHB patients undergone NA monotherapy for over 96 weeks. Patients were categorized into maintained virological response (MVR) and LLV groups based on hepatitis B virus (HBV) DNA levels. The study assessed LF using various markers and methods, including chitinase 3-like 1 protein (CHI3L1), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and transient elastography. Results: Analysis was conducted on 92 CHB patients, categorized into LLV (n=42) and MVR (n=50) groups, following the exclusion of 101 patients for various reasons. Significant findings included lower baseline HBV DNA in MVR (<20 IU/mL) compared to LLV (67.8 IU/mL, P<0.001) and different AST/ALT ratios (LLV: 1.1, MVR: 1.36, P=0.011). LF was assessed using CHI3L1, FIB-4, and APRI, with LLV showing a higher baseline CHI3L1 (LLV:83.3 ng/mL vs MVR: 54.5 ng/mL, P=0.016) and scores compared to MVR, indicative of fibrosis. CHI3L1 levels in LLV were higher at baseline and weeks 48, 72, and 96 than MVR, with significance at baseline (P=0.038) and week 48 (P=0.034). Liver stiffness measurement (LSM) showed a time-dependent decline in both groups but no significant intergroup differences. Conclusion: Non-invasive monitoring of CHB patients who have received treatment indicates that LLV contributes to the progression of LF, necessitating proactive adjustment of antiviral treatment strategies.

Strain-Triggered Distinct Oxygen Evolution Reaction Pathway in Two-Dimensional Metastable Phase IrO2 via CeO2 Loading.

A strain engineering strategy is crucial for designing a high-performance catalyst. However, how to control the strain in metastable phase two-dimensional (2D) materials is technically challenging due to their nanoscale sizes. Here, we report that cerium dioxide (CeO2) is an ideal loading material for tuning the in-plane strain in 2D metastable 1T-phase IrO2 (1T-IrO2) via an in situ growth method. Surprisingly, 5% CeO2 loaded 1T-IrO2 with 8% compressive strain achieves an overpotential of 194 mV at 10 mA cm-2 in a three-electrode system. It also retained a high current density of 900 mA cm-2 at a cell voltage of 1.8 V for a 400 h stability test in the proton-exchange membrane device. More importantly, the Fourier transform infrared measurements and density functional theory calculation reveal that the CeO2 induced strained 1T-IrO2 directly undergo the *O-*O radical coupling mechanism for O2 generation, totally different from the traditional adsorbate evolution mechanism in pure 1T-IrO2. These findings illustrate the important role of strain engineering in paving up an optimal catalytic pathway in order to achieve robust electrochemical performance.

The physiological and pathological roles of RNA modifications in T cells.

RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.

Pharmacokinetics and safety of GST-HG171, a novel 3CL protease inhibitor, in Chinese subjects with impaired and normal liver function.

GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C-like (3CL) protease inhibitor that was recently approved for treating mild to moderate coronavirus disease 2019 patients in China. Since cytochrome P450 (CYP) enzymes, primarily CYP3A, are the main metabolic enzymes of GST-HG171, hepatic impairment may affect its pharmacokinetic (PK) profile. Aiming to guide clinical dosing for patients with hepatic impairment, this study, using a non-randomized, open-label, single-dose design, assessed the impact of hepatic impairment on the PK, safety, and tolerability of GST-HG171. Patients with mild and moderate hepatic impairment along with healthy subjects were enrolled (n = 8 each), receiving a single oral dose of 150 mg GST-HG171, with concurrent administration of 100 mg ritonavir to sustain CYP3A inhibition before and after GST-HG171 administration (-12, 0, 12, and 24 hours). Compared to subjects with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for GST-HG171's maximum plasma concentration (Cmax), area under the concentration-time curve up to the last quantifiable time (AUC0-t), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) in subjects with mild hepatic impairment were 1.14 (0.99, 1.31), 1.07 (0.88, 1.30), and 1.07 (0.88, 1.29), respectively. For moderate hepatic impairment, the ratios were 0.87 (0.70, 1.07), 0.82 (0.61, 1.10), and 0.82 (0.61, 1.10), respectively. Hepatic impairment did not significantly alter GST-HG171's peak time (Tmax) and elimination half-life (T1/2). GST-HG171 exhibited good safety and tolerability in the study. Taken together, mild to moderate hepatic impairment minimally impacted GST-HG171 exposure, suggesting no need to adjust GST-HG171 dosage for patients with mild to moderate hepatic impairment in the clinic.Clinical TrialsRegistered at ClinicalTrials.gov (NCT06106113).

Clinical and hematological characteristics of children infected with the omicron variant of SARS-CoV-2: role of the combination of the neutrophil: lymphocyte ratio and eosinophil count in distinguishing severe COVID-19.

Purpose: Investigate the clinical/hematological characteristics of children infected with the Omicron variant of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and identify an effective indicator to distinguish coronavirus disease 2019 (COVID-19) severity in children. Methods: A retrospective study was conducted through electronic medical records from pediatric patients. The demographic, clinical, and routine blood test (RBT) features of children diagnosed by real-time PCR for SARS-CoV-2 were collected. Results: Data of 261 patients were analyzed. The most common abnormality shown by RBTs was increased monocyte count (68%). Children had "mild-moderate" or "severe" forms of COVID-19. Prevalence of abnormal neutrophil count (p = 0.048), eosinophil count (p = 0.006), mean corpuscular volume (p = 0.033), mean platelet volume (p = 0.006), platelet-large cell ratio (p = 0.043), and red blood cell distribution width-standard deviation (p = 0.031) were significantly different in the two types. A combination of the neutrophil: lymphocyte ratio (NLR) and eosinophil count for diagnosing severe COVID-19 presented the largest AUC (0.688, 95% CI = 0.599-0.777; p < 0.001), and the AUC increased with a decrease in age. Conclusions: Combination of the NLR and eosinophil count might be a promising indicator for identifying severe COVID-19 in children at infection onset.

Left atrial strain parameters to predicting elevated left atrial pressure in patients with atrial fibrillation.

OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Acetyl-11-keto-ß-boswellic acid restrains the progression of synovitis in osteoarthritis via the Nrf2/HO-1 pathway.

Synovial inflammation plays a key role in osteoarthritis (OA) pathogenesis. Fibroblast-like synoviocytes (FLSs) represent a distinct cell subpopulation within the synovium, and their unique phenotypic alterations are considered significant contributors to inflammation and fibrotic responses. The underlying mechanism by which acetyl-11-keto-ß-boswellic acid (AKBA) modulates FLS activation remains unclear. This study aims to assess the beneficial effects of AKBA through both in vitro and in vivo investigations. Network pharmacology evaluation is used to identify potential targets of AKBA in OA. We evaluate the effects of AKBA on FLSs activation in vitro and the regulatory role of AKBA on the Nrf2/HO-1 signaling pathway. ML385 (an Nrf2 inhibitor) is used to verify the binding of AKBA to its target in FLSs. We validate the in vivo efficacy of AKBA in alleviating OA using anterior cruciate ligament transection and destabilization of the medial meniscus (ACLT+DMM) in a rat model. Network pharmacological analysis reveals the potential effect of AKBA on OA. AKBA effectively attenuates lipopolysaccharide (LPS)-induced abnormal migration and invasion and the production of inflammatory mediators, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS) in FLSs, contributing to the restoration of the synovial microenvironment. After treatment with ML385, the effect of AKBA on FLSs is reversed. In vivo studies demonstrate that AKBA mitigates synovial inflammation and fibrotic responses induced by ACLT+DMM in rats via activation of the Nrf2/HO-1 axis. AKBA exhibits theoretical potential for alleviating OA progression through the Nrf2/HO-1 pathway and represents a viable therapeutic candidate for this patient population.

Sugar import mediated by sugar transporters and cell wall invertases for seed development in Camellia oleifera.

Seed development and yield depend on the transport and supply of sugar. However, an insufficient supply of nutrients from maternal tissues to embryos results in seed abortion and yield reduction in Camellia oleifera. In this study, we systematically examined the route and regulatory mechanisms of sugar import into developing C. oleifera seeds using a combination of histological observations, transcriptome profiling, and functional analysis. Labelling with the tracer carboxyfluorescein revealed a symplasmic route in the integument and an apoplasmic route for postphloem transport at the maternal-filial interface. Enzymatic activity and histological observation showed that at early stages [180-220 days after pollination (DAP)] of embryo differentiation, the high hexose/sucrose ratio was primarily mediated by acid invertases, and the micropylar endosperm/suspensor provides a channel for sugar import. Through Camellia genomic profiling, we identified three plasma membrane-localized proteins including CoSWEET1b, CoSWEET15, and CoSUT2 and one tonoplast-localized protein CoSWEET2a in seeds and verified their ability to transport various sugars via transformation in yeast mutants and calli. In situ hybridization and profiling of glycometabolism-related enzymes further demonstrated that CoSWEET15 functions as a micropylar endosperm-specific gene, together with the cell wall acid invertase CoCWIN9, to support early embryo development, while CoSWEET1b, CoSWEET2a, and CoSUT2 function at transfer cells and chalazal nucellus coupled with CoCWIN9 and CoCWIN11 responsible for sugar entry in bulk into the filial tissue. Collectively, our findings provide the first comprehensive evidence of the molecular regulation of sugar import into and within C. oleifera seeds and provide a new target for manipulating seed development.

Pan-cancer analysis and the oncogenic role of Glypican 1 in hepatocellular carcinoma.

Recent studies indicate that Glypican 1 (GPC-1) is aberrantly expressed and plays a key role in certain cancers, but little is known in the hepatocellular carcinoma. Raw data from TCGA, GTEx and TIMER databases were utilized to comprehensively analyze GPC-1 expression landscape in pan-cancer, and the biological function of GPC-1 was investigated in liver cancer cells. The results revealed that GPC-1 is highly expressed in HCC, negatively correlated with survival, and also positively correlated with immune infiltration and clinical stage. Furthermore, GPC-1 promoted cell proliferation and inhibited apoptosis in the HCC cell lines. WGCNA analysis and HCCDB database revealed that Akt acted as a key molecule related to GPC-1, influencing biological functions and regulating cell malignant behaviors via the AKT signaling pathway. In conclusion, our findings provide a relatively comprehensive understanding of the oncogenic role of GPC-1 in HCC, implying that GPC-1 could serve as an innovative therapeutic target.