Chemoradiotherapy plus tislelizumab for mismatch repair proficient rectal cancer with supraclavicular lymph node metastasis: A case report.

BACKGROUND: According to the latest report, colorectal cancer is still one of the most prevalent cancers, with the third highest incidence and mortality worldwide. Treatment of advanced rectal cancer with distant metastases is usually unsatisfactory, especially for mismatch repair proficient (pMMR) rectal cancer, which leads to poor prognosis and recurrence. CASE SUMMARY: We report a case of a pMMR rectal adenocarcinoma with metastases of multiple lymph nodes, including the left supraclavicular lymph node, before treatment in a 70-year-old man. He received full courses of chemoradiotherapy (CRT) followed by 4 cycles of programmed death 1 inhibitor Tislelizumab, and a pathologic complete response (pCR) was achieved, and the lesion of the left supraclavicular lymph node also disappeared. CONCLUSION: pMMR advanced rectal cancer with preserved intact distant metastatic lymph nodes may benefit from full-course CRT combined with immunotherapy.

Defective state regulation of Ru-doped Nb2O5 boosts fast lithium storage.

Breaking through the limitations of lithium-ion transmission is imperative for high-power rechargeable batteries. As a promising anode material for fast-charging lithium-ion batteries (LIBs), niobium pentoxide (Nb2O5) has garnered considerable research attention due to its exceptional rate performance, stable lithium storage performance and high safety attributes. Nevertheless, the limited intrinsic conductivity of Nb2O5, coupled with its structural degradation during the cycling process, imposes constraints on its viability as a commercially viable electrode material. Herein, a ruthenium (Ru) doping method is employed to regulate the oxygen defects and the interlayer spacing of the tetragonal Nb2O5 (M-Nb2O5), offering superior reaction kinetics, higher stability for lithium storage sites and more unobstructed lithium-ion transport channels. Ru-doped Nb2O5 (RNO) manifests excellent electrochemical properties, including remarkable rate capacity (166 mAh/g at 80C), reversible capacity (246.98 mAh/g at 0.5C), improved initial Coulombic efficiency (95.77 % compared to 81.44 % of the pure sample) and cycling stability (maintaining a capacity of 113.5 mAh/g at 10C for 2,000 cycles). The enhancement mechanism of Ru doping on the structural stability and ion transport kinetics in tetragonal Nb2O5 is comprehensively elucidated through diverse electrochemical analyses and in-situ techniques.

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer.

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894-0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489-0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.

Spinal Cord Injury Without Radiographic Abnormalities Caused By Rotation Stretching Injury Manifesting As Brown- Sequard Syndrome: A Case Report.

Spinal cord injury without radiographic abnormality (SCIWORA) is a term that denotes clinical symptoms of traumatic myelopathy without radiographic or computed tomographic features of vertebral fracture or instability. However, SCIWORA in adults is very rare, especially that involving the thoracic spine. We describe the case of a 38-year-old man who complained of weakness in the right lower extremity for two hours. The injury occurred due to rapid spinal cord rotation-stretching. The patient was diagnosed with SCIWORA at the T4 level, manifesting as Brown-Sequard syndrome (BBS). Finally, he was able to walk independently without assistance after two-month treatment. SCIWORA due to spinal cord rotation-stretching injury, manifesting as BSS, is a very rare mechanism of injury. When X-ray and CT scans rule out the diagnosis of spinal fractures, SCIWORA should be suspected. We recommend that clinicians should have a comprehensive and systematic understanding of this disease to greatly reduce misdiagnosis and improve the level of treatment.

Hounsfield Unit for Evaluating Bone Mineral Density and Strength: Variations in Measurement Methods.

OBJECTIVE: To assess the consistency and accuracy of various measurements of the Hounsfield unit (HU) in lumbar vertebrae. METHODS: The study reviewed lumbar spine computed tomography images of 60 postmenopausal women aged >50 years. A total of 240 vertebrae were measured and analyzed for the variations of HU values in different sections and regions. Investigated the relationship between HU values of the lumbar spine under different measurements and dual-energy X-ray absorptiometry results and the ability to identify patients with osteoporosis. RESULTS: HU values measured in midsagittal (r = 0.763), midcoronal (r = 0.768), and midaxial (r = 0.786) sections exhibited a strong positive correlation with dual-energy X-ray absorptiometry T-scores. HU values measured in midsagittal and midaxial sections of the vertebral body were in good agreement (P > 0.1), but decreased in the midcoronal (P < 0.001). HU values in the middle of the vertebral body were significantly higher than in the near end plate (P < 0.001). HU values varied between L1 and L4 vertebrae, but all had a good ability to identify osteoporosis and did not differ significantly in screening ability (P > 0.05). CONCLUSIONS: An averaged HU value in axial multilevel is a comprehensive assessment of vertebral bone density. Using the HU value of the lumbar spine can help identify patients with osteoporosis, and the screening ability does not differ significantly across vertebral segments.

Vancomycin-loaded silk fibroin microspheres in an injectable hydrogel for chronic osteomyelitis therapy.

Introduction: Chronic osteomyelitis remains a clinical challenge in orthopedics. Methods: In this study, silk fibroin microspheres (SFMPs) loaded with vancomycin are entrapped in an injectable silk hydrogel to form a vancomycin delivery system for treatment of chronic osteomyelitis. Results and Discussion: Vancomycin showed continuous release from the hydrogel for up to 25 days. The hydrogel shows strong antibacterial activity against both Escherichia coli and Staphylococcus aureus and a long antibacterial duration of 10 days without a decrease in the antibacterial effect. The injection of vancomycin-loaded silk fibroin microspheres entrapped in the hydrogel into the infected site of rat tibia reduced bone infection and improved bone regeneration compared with other treatment groups. Conclusion: Thus, the composite SF hydrogel features a sustained-release profile and good biocompatibility, making it promising for application in osteomyelitis treatment.

Natural pressure drainage versus negative pressure drainage following transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degeneration disease: a prospective cohort study.

OBJECTIVE: To comprehensively compare the perioperative data and clinical outcomes of natural pressure drainage (NAPD) and negative pressure drainage (NEPD) following transforaminal lumbar interbody fusion (TLIF) for the treatment of lumbar degeneration disease. METHODS: Between January 2021 and December 2021, 203 patients in our hospital who underwent single- or two-segment TLIF were assigned to the NAPD group (112 patients) or the NEPD group (91 patients) based on different postoperative drainage methods. Between the two groups, comparisons were made regarding the demographics, intraoperative and postoperative data, patient-reported outcomes, and complications. RESULTS: The NAPD group experienced less overall drainage and fewer postoperative drainage days (157.89 vs. 318.49 ml/249.54 vs. 589.43 ml, 2.00 vs. 2.67 days/2.04 vs. 2.74 days, P < 0.001) than the NEPD group. The NAPD group has a higher rate of overall hidden blood loss (HBL) than the NEPD group (63.98% vs. 51.90%/65.80% vs. 48.11%, P < 0.001); HBL, however, did not significantly differ between the two groups (P > 0.05). In two-segment surgery, the postoperative hemoglobin (HGB) levels were higher in the NAPD group (99.67 vs. 92.69 g/L, P < 0.05), but there was no difference in single-segment surgery (P > 0.05). Regardless of whether single- or two-segment surgery was performed, the NAPD group had a lower HGB level loss (18.81% vs. 21.63%/26.35% vs. 32.08%, P < 0.05). There was no discernible difference between the two groups in the visual analog scale (VAS) scores for symptomatic epidural hematoma, postoperative body temperature, low back and leg pain, or incision infection (P > 0.05). CONCLUSION: NAPD did not increase postoperative complications but did significantly reduce postoperative drainage volume and the risk of anemia. We show that, when compared to NEPD, NAPD may be a better option for patients following TLIF.

The emerging role of neutrophil extracellular traps in cancer: from lab to ward.

Neutrophil extracellular traps (NETs) are web-like structures derived from neutrophils, which typically consist of DNA, released from the nucleus or mitochondria, and decorated with histones and granule proteins. They are well known as an important structure in innate immunity to eliminate pathogenic bacteria, similar to neutrophils. Initially, NETs are reported to take part in the progression of inflammatory diseases; now, they have also been implicated in the progression of sterile inflammation such as autoimmune disease, diabetes, and cancer. In this review, we will describe the recent studies which have investigated the role of NETs in the development of cancer, especially metastasis. We also prescribe the strategies for targeting NETs in the multiple cancer types, which suggest that NETs are a promising treatment for cancer patients.

Obesity and endocrine-related cancer: The important role of IGF-1.

Obesity is increasingly becoming a global epidemic of concern and is considered a risk factor for several endocrine-related cancers. Moreover, obesity is associated with cancer development and poor prognosis. As a metabolic abnormality, obesity leads to a series of changes in insulin, IGF-1, sex hormones, IGFBPs, and adipokines. Among these factors, IGF-1 plays an important role in obesity-related endocrine cancers. This review describes the role of obesity in endocrine-related cancers, such as prostate cancer, breast cancer and pancreatic cancer, focusing on the mechanism of IGF-1 and the crosstalk with estrogen and adipokines. In addition, this review briefly introduces the current status of IGF-1R inhibitors in clinical practice and shows the prospect of IGF-1R inhibitors in combination with other anticancer drugs.

Vertebral bone quality score provides preoperative bone density assessment for patients undergoing lumbar spine surgery: a retrospective study.

OBJECTIVE: The novel MRI-based vertebral bone quality (VBQ) score has been described as an opportunistic screening tool for osteoporosis, but the stability and practical value of this score deserve further investigation. The purpose of this study was to assess whether preoperative VBQ scores could assist in identifying reduced bone mineral density (BMD) or osteoporosis and evaluating the consistency between MRI systems with different field strengths. METHODS: The VBQ scores of the patients who underwent surgery for lumbar disc herniation and the single-level VBQ scores of each L1-4 vertebral body were measured and calculated with preoperative lumbar MRI noncontrast T1-weighted phases. The VBQ scores were evaluated for correlation analysis using dual-energy x-ray absorptiometry (DEXA) T-scores. The receiver operating characteristic (ROC) curve was used to evaluate the ability of the VBQ scores to identify patients with reduced BMD and with osteoporosis. Differences in CSF measurements at different levels of L1-4 were compared. Twenty-four patients who had been examined using another MRI machine were used as controls to test the interdevice agreement of the VBQ scores. RESULTS: The study included 100 patients with mean VBQ scores of 2.81 ± 0.28 (normal BMD), 3.06 ± 0.36 (osteopenia), and 3.43 ± 0.37 (osteoporosis). VBQ scores differed significantly between BMD subgroups (p < 0.001). The Pearson correlation coefficient showed a moderate negative linear correlation between novel VBQ scores and the lowest DEXA T-scores (r = -0.524). ROC analysis showed good discrimination of VBQ scores in patients with reduced BMD (area under the curve [AUC] 0.793) and with osteoporosis (AUC 0.810). The diagnostic thresholds of reduced BMD and osteoporosis according to the maximum Youden index were 3.06 (sensitivity 0.636, specificity 0.870, positive predictive value [PPV] 0.942, negative predictive value [NPV] 0.417) and 3.05 (sensitivity 0.875, specificity 0.618, PPV 0.519, NPV 0.913), respectively. CSF measurements at the L2, L3, and L4 levels were essentially identical and did not significantly affect the final VBQ scores (p > 0.05), whereas CSF measurements at the L1 level were found to be heterogeneous (p < 0.001). No significant differences were found in VBQ scores between the same brand of MRI machines at different field strengths (1.5 and 3.0 T, p = 0.107). CONCLUSIONS: The new VBQ score provides an additional screening opportunity for preoperative BMD assessment. A VBQ score < 3.05 essentially excludes osteoporosis, whereas a VBQ score ≥ 3.05 (especially ≥ 3.06) suggests the need for further examination. The VBQ score is comparable between different MRI systems.

PEDOT-intercalated NH4V3O8 nanobelts as high-performance cathode materials for potassium ion batteries.

Potassium ion batteries (PIBs) have great potential to replace lithium ion batteries (LIBs) for large-scale energy storage applications because of the low cost and earth abundance of potassium resources. However, it is critically challenging to exploit an appropriate cathode material to accommodate the large size of K+. Herein, a conducting polymer (PEDOT) intercalation method is utilized to tailor the interlayer spacing of NH4V3O8 nanobelts from 7.8 Å to 10.8 Å, and afford rich oxygen vacancies inside the vanadate, thus enhancing its electronic conductivity and accelerating the K+ insertion/extraction kinetics. Benefiting from these features, PEDOT-intercalated NH4V3O8 (PNVO) nanobelts deliver an improved capacity of 87 mA h g-1 at 20 mA g-1, high rate capability of 51 mA h g-1 at 500 mA g-1, and a stable cycle life (capacity retention of 92.5 % after 100 cycles at 50 mA g-1). Even cycled at 200 mA g-1, PNVO nanobelts feature a long cycle life over 300 cycles with a capacity retention of 71.7 %. This work is of great significance for exploitation of PIBs cathode with improved electrochemical performance through pre-intercalation and defect engineering.

Neutrophil Extracellular Trap is Surrogate Biomarker for Prognosis and Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

Purpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms. Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3. Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial-mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response. Conclusion: NET was an independent prognostic factor in LARC that were associated with patients' survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.

Peritumoral tertiary lymphoid structure and tumor stroma percentage predict the prognosis of patients with non-metastatic colorectal cancer.

Background: Tertiary lymphoid structures (TLSs) are crucial in promoting and maintaining positive anti-tumor immune responses. The tumor stroma has a powerful immunosuppressive function that could exclude tumor-infiltrating lymphocytes from the tumor beds and lead to a "cold" phenotype. TLSs and tumor stroma percentage (TSP) are significantly associated with the prognosis of patients with certain cancers. However, the exact roles of TLSs and TSP and their intrinsic relationship are still largely unknown in colorectal cancer (CRC). Methods: TLSs and TSP were assessed using hematoxylin-eosin (H&E) and/or immunohistochemistry (IHC) staining from 114 CRC patients in the training set and 60 CRC patients in the external validation set. The correlation between TILs, TLS and clinicopathological characteristics and their prognostic values were assessed. Finally, we plotted a Nomogram including the TLS, TSP and tumor-node-metastasis (TNM) stage to predict the probability of recurrence-free survival (RFS) at 2- and 5-years in non-metastatic colorectal cancer (nmCRC) patients. Results: Peritumoral TLS (P-TLS), intratumoral TLS (In-TLS) and high TSP (H-TSP, >50%) were present in 99.1%, 26.3% and 41.2% patients, respectively. H-TSP tumor tends to be associated with lower P-TLS density (P =0.0205). The low P-TLS density (< 0.098/mm2) was significantly associated with reduced RFS (HR=6.597 95% CI: 2.882-15.103, P <0.001) and reduced overall survival (OS) (HR=6.628 95% CI: 2.893-15.183, P < 0.001) of nmCRC patients. In-TLS was not of significance in evaluating the clinical outcomes of nmCRC patients. H-TSP was significantly associated with reduced RFS (HR=0.126 95% CI: 0.048-0.333, P <0.001) and reduced OS (HR=0.125 95% CI: 0.047-0.332, P <0.001) of nmCRC patients. The 5-year RFS of the high P-TLS, low-TLS, H-TSP, and L-TSP groups were 89.7%, 47.2%, 53.2%, and 92.5%, respectively. The P-TLS density, TSP and TNM stage were independent prognosis factors of nmCRC patients. The Nomogram, including the P-TLS density, TSP and TNM stage, outperformed the TNM stage. Conclusions: High P-TLS density and low TSP (L-TSP) were independent and favorable prognostic factors of nmCRC patients, which might provide new directions for targeted therapy in the CRC tumor microenvironment, especially the tumor immune microenvironment.

Palladium-Catalyzed Regio- and Stereoselective Coupling of Alkynylsulfones with Alkenes: Access to Dichlorinated Vinyl Sulfones.

A palladium-catalyzed coupling reaction of alkynylsulfones with alkenes has been described, which provides an efficient and practical entry to various functionalized dichlorinated vinyl sulfones. This method features excellent regio- and stereoselectivities, good functional group compatibility, as well as mild reaction conditions. Mechanistic studies suggest that the reaction goes through sequential syn-chloropalladation, alkene insertion, and C(sp3)-Cl bond formation processes, and the sulfonyl group is crucial to the stereoselectivity control of the reaction.

Enhanced crystallization and storage stability of mechanical properties of poly(hydroxyalkanoate)s in the presence of hydrazide compounds with different configurations.

Slow crystallization rates and poor storage stability of mechanical properties limit the widespread use of biosynthesized poly(hydroxyalkanoate)s (PHA). Hydrazide compounds (HCn) with a formula of C6H5CONHNHCO(CH2)nCONHNHCOC6H5 (n = 4 and 8) were used as PHA nucleating agents to improve the crystallization and mechanical properties. The effects of HCn structure and self-assembly on the crystallization kinetics and nucleation efficiency of PHA were systematically investigated. Both HCns can be dissolved in the PHA matrix at high temperatures and then self-assemble into rod-like structures to induce crystallization of PHA. The nucleation efficiency of HC8 is much better than that of HC4 at low subcooling. With only 0.75 wt% HC8, the crystallization half-life time t1/2 of PHA at 100 °C decreased by 91 % and the degree of crystallinity increased to 38.2 % with a large number of tiny nuclei. Moreover, storage stability of mechanical properties of PHA was greatly improved due to the better crystallization ability. Therefore, this work provides a basis for the design of high-efficiency nucleating agents for PHA, which is expected to improve the mechanical properties and expand the application fields of PHA.

Synthesis of 2,5-disubstituted selenophenes via a copper-catalyzed regioselective [2+2+1] cyclization of terminal alkynes and selenium.

Herein, a straightforward method for the synthesis of 2,5-disubstituted selenophenes via [2+2+1] cyclization of easily accessible terminal alkynes and elemental selenium has been developed. This reaction features high atom- and step-economy, excellent regioselectivity, good functional group tolerance and the use of stable and non-toxic selenium as a selenium source. A series of control experiments suggests that the reaction might undergo Glaser coupling reaction of two molecules of alkynes, followed by insertion of H2Se and subsequent cyclization. Moreover, the newly formed products can be further converted to diverse conjugated selenophene-based derivatives, demonstrating their potential applications in organic synthesis and materials science.

Enabling high energy lithium metal batteries via single-crystal Ni-rich cathode material co-doping strategy.

High-capacity Ni-rich layered oxides are promising cathode materials for secondary lithium-based battery systems. However, their structural instability detrimentally affects the battery performance during cell cycling. Here, we report an Al/Zr co-doped single-crystalline LiNi0.88Co0.09Mn0.03O2 (SNCM) cathode material to circumvent the instability issue. We found that soluble Al ions are adequately incorporated in the SNCM lattice while the less soluble Zr ions are prone to aggregate in the outer SNCM surface layer. The synergistic effect of Al/Zr co-doping in SNCM lattice improve the Li-ion mobility, relief the internal strain, and suppress the Li/Ni cation mixing upon cycling at high cut-off voltage. These features improve the cathode rate capability and structural stabilization during prolonged cell cycling. In particular, the Zr-rich surface enables the formation of stable cathode-electrolyte interphase, which prevent SNCM from unwanted reactions with the non-aqueous fluorinated liquid electrolyte solution and avoid Ni dissolution. To prove the practical application of the Al/Zr co-doped SNCM, we assembled a 10.8 Ah pouch cell (using a 100 µm thick Li metal anode) capable of delivering initial specific energy of 504.5 Wh kg-1 at 0.1 C and 25 °C.

Implantation of nanofibrous silk scaffolds seeded with bone marrow stromal cells promotes spinal cord regeneration (6686 words).

Spinal cord injury (SCI) is a common pathology often resulting in permanent loss of sensory, motor, and autonomic function. Numerous studies in which stem cells have been transplanted in biomaterial scaffolds into animals have demonstrated their considerable potential for recovery from SCI. In the present study, a three-dimensional porous silk fibroin (SF) scaffold with a mean pore size of approximately 383 µm and nanofibrous structure was fabricated, the silk scaffold enabling the enhanced attachment and proliferation of bone marrow stromal cells (BMSCs). Investigation of its therapeutic potential was conducted by implantation of the nanofibrous SF scaffold seeded with BMSCs into a transected spinal cord model. Recovery of the damaged spinal cord was significantly improved after 2 months, compared with a non-nanofibrous scaffold, in combination with decreased glial fibrillary acidic protein (GFAP) expression and improved axonal regeneration at the site of injury. Furthermore, elevated Basso-Beattie-Bresnahan (BBB) scores indicated greatly improved hindlimb movement. Together, these results demonstrate that transplantation of neural scaffolds consisting of nanofibrous SF and BMSCs is an attractive strategy for the promotion of functional recovery following SCI.

A Review of Monitoring Methods for Cerebral Blood Oxygen Saturation.

In recent years, cerebral blood oxygen saturation has become a key indicator during the perioperative period. Cerebral blood oxygen saturation monitoring is conducive to the early diagnosis and treatment of cerebral ischemia and hypoxia. The present study discusses the three most extensively used clinical methods for cerebral blood oxygen saturation monitoring from different aspects: working principles, relevant parameters, current situations of research, commonly used equipment, and relative advantages of different methods. Furthermore, through comprehensive comparisons of the methods, we find that near-infrared spectroscopy (NIRS) technology has significant potentials and broad applications prospects in terms of cerebral oxygen saturation monitoring. Despite the current NIRS technology, the only bedside non-invasive cerebral oxygen saturation monitoring technology, still has many defects, it is more in line with the future development trend in the field of medical and health, and will become the main method gradually.

Secretory Galectin-3 promotes hepatic steatosis via regulation of the PPARγ/CD36 signaling pathway.

Galectin-3 (Gal3) is an essential regulator of a number of metabolic disorders. Previous studies have established that Gal3 is a positive regulator of inflammation, fibrosis, and insulin resistance. However, its function in the early pathogenesis of hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) remains unresolved. Here, we demonstrate the presence of significantly upregulated extracellular concentrations of Gal3 in the fatty livers of high-fat diet (HFD)-induced mice. Systemic inhibition of Gal3 by injection of TD139 reduced the accumulation of lipid in the livers of HFD-fed mice, accompanied by the decreased expression of CD36 and peroxisome proliferator-activated receptor-gamma (PPARγ). Treatment with Gal3 protein elicited the opposite response in palmitic acid (PA)-induced HepG2 hepatocytes. It was additionally discovered that Gal3 positively regulates CD36 transcription by increased activation of PPARγ, thereby increasing fatty acid uptake, resulting in hepatic steatosis. In conclusion, the present study confirmed the roles of Gal3 in hepatic lipid metabolism in both in vitro and in vivo studies and revealed that Gal3 is a secretory protein that promotes hepatic steatosis through the PPARγ-CD36-dependent pathway, suggesting that targeting Gal3 may represent a potential therapeutic approach for the treatment of NAFLD and related metabolic disorders.