The fabrication of ZIF-L derived ZnS/MoS2@NC anode materials for remarkable lithium-ion storage.

The enhancement of electrochemical performance in lithium-ion batteries can be achieved through the incorporation of MoS2 with carbon materials and various metal sulfides. In this investigation, a MoS2/ZnS heterostructure was devised incorporating a two-dimensional nitrogen-doped carbon nanosheet (NC) backbone. The synthesis of ZnMo-ZIF-L precursors was achieved by introducing a Mo source in a 1:1 molar ratio during ZIF-L synthesis. Subsequent to high-temperature carbonization and vulcanization treatment, ZnS/MoS2@NC composite materials were successfully synthesized. Compared to the unvulcanized ZnO/MoO3@NC and MoS2 samples, the ZnS/MoS2@NC composite exhibits remarkable lithium storage performance. At a current density of 500 mA g-1, the initial discharge specific capacity is 2547 mAh g-1, with an initial charge specific capacity of 1674 mAh g-1, resulting in a first Coulombic efficiency of 65.76%. Furthermore, this composite material demonstrates optimal rate capabilities and a significant pseudocapacitance contribution. The nitrogen-doped carbon framework effectively mitigates volume effects, while the heterostructural design provides more active sites for lithium ions, thereby enhancing lithium storage performance.

PROTAC-mediated vimentin degradation promotes terminal erythroid differentiation of pluripotent stem cells.

BACKGROUND: Human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), can undergo erythroid differentiation, offering a potentially invaluable resource for generating large quantities of erythroid cells. However, the majority of erythrocytes derived from hPSCs fail to enucleate compared with those derived from cord blood progenitors, with an unknown molecular basis for this difference. The expression of vimentin (VIM) is retained in erythroid cells differentiated from hPSCs but is absent in mature erythrocytes. Further exploration is required to ascertain whether VIM plays a critical role in enucleation and to elucidate the underlying mechanisms. METHODS: In this study, we established a hESC line with reversible vimentin degradation (dTAG-VIM-H9) using the proteolysis-targeting chimera (PROTAC) platform. Various time-course studies, including erythropoiesis from CD34+ human umbilical cord blood and three-dimensional (3D) organoid culture from hESCs, morphological analysis, quantitative real-time PCR (qRT-PCR), western blotting, flow cytometry, karyotyping, cytospin, Benzidine-Giemsa staining, immunofluorescence assay, and high-speed cell imaging analysis, were conducted to examine and compare the characteristics of hESCs and those with vimentin degradation, as well as their differentiated erythroid cells. RESULTS: Vimentin expression diminished during normal erythropoiesis in CD34+ cord blood cells, whereas it persisted in erythroid cells differentiated from hESC. Depletion of vimentin using the degradation tag (dTAG) system promotes erythroid enucleation in dTAG-VIM-H9 cells. Nuclear polarization of erythroblasts is elevated by elimination of vimentin. CONCLUSIONS: VIM disappear during the normal maturation of erythroid cells, whereas they are retained in erythroid cells differentiated from hPSCs. We found that retention of vimentin during erythropoiesis impairs erythroid enucleation from hPSCs. Using the PROTAC platform, we validated that vimentin degradation by dTAG accelerates the enucleation rate in dTAG-VIM-H9 cells by enhancing nuclear polarization.

Straw Tar Epoxy Resin for Carbon Fiber-Reinforced Plastic: A Review.

The massive consumption of fossil fuels has led to the serious accumulation of carbon dioxide gas in the atmosphere and global warming. Bioconversion technologies that utilize biomass resources to produce chemical products are becoming widely accepted and highly recognized. The world is heavily dependent on petroleum-based products, which may raise serious concerns about future environmental security. Most commercially available epoxy resins (EPs) are synthesized by the condensation of bisphenol A (BPA), which not only affects the human endocrine system and metabolism, but is also costly to produce and environmentally polluting. In some cases, straw tar-based epoxy resins have been recognized as potential alternatives to bisphenol A-based epoxy resins, and are receiving increasing attention due to their important role in overcoming the above problems. Using straw tar and lignin as the main raw materials, phenol derivatives were extracted from the middle tar instead of bisphenol A. Bio-based epoxy resins were prepared by replacing epichlorohydrin with epoxylated lignin to press carbon fiber sheets, which is a kind of bio-based fine chemical product. This paper reviews the research progress of bio-based materials such as lignin modification, straw pyrolysis, lignin epoxidation, phenol derivative extraction, and synthesis of epoxy resin. It improves the performance of carbon fiber-reinforced plastic (CFRP) while taking into account the ecological and environmental protection, so that the epoxy resin is developed in the direction of non-toxic, harmless and high-performance characteristics, and it also provides a new idea for the development of bio-based carbon fibers.

Risk factors for acute pancreatitis post percutaneous transhepatic biliary stenting in patients with distal malignant obstruction.

Background: Percutaneous transhepatic biliary stenting (PTBS) is an effective treatment for distal malignant biliary obstruction (MBO). Postoperative acute pancreatitis (AP) is a dangerous complication of this procedure. This study sought to investigate the risk factors for AP after PTBS. Methods: A total of 463 patients who underwent PTBS to treat suspected MBO from October 2012 to October 2021 were enrolled in this retrospective study. Among them, 26 individuals met the diagnostic criteria for postoperative pancreatitis following PTBS. The incidence of AP at 1 month postoperatively was recorded and analyzed. Several risk factors for AP were analyzed, and the odds ratios (ORs) were calculated by univariate and multivariate logistic analyses. Results: The incidence of AP after PTBS was 10.88% (26/239). The results of the multivariate analyses showed that repeated bile duct hemorrhage (OR =14.370, P=0.0001), intraoperative dilation (OR =7.848, P=0.0003), an operation time >50 min (OR =5.783, P=0.0009), and previous endoscopic intervention (OR =5.468, P=0.0021) were correlated with a high incidence of AP, while sex, age, time to biliary obstruction, body mass index, Eastern Cooperative Oncology Group score, previous anticancer treatments, forceps biopsy, obstruction length, stent size, contrast volume, operators, 125I strand placement, and blood parameters were not significantly correlated with AP (all P>0.05). Conclusions: A long operation time, intraoperative dilation, repeated bile duct hemorrhage, and previous endoscopic intervention were independent risk factors for AP. These factors should be considered by clinicians in future practice.

Promoting medication compliance in epileptic children: a cross sectional survey.

BACKGROUND: Compliance with medication is crucial for the favorable prognosis of children with epilepsy. The objective of this study was to assess the determinants of medication compliance and to construct a predictive model for the risk of non-compliance among pediatric epilepsy patients. METHODS: The study included children diagnosed with epilepsy and treated at our hospital between February 1 and September 30, 2023. We evaluated the demographic characteristics and medication compliance profiles of these patients. The predictive model's performance was assessed using the receiver operating characteristic (ROC) curve to determine its sensitivity and specificity. RESULTS: A total of 168 children with epilepsy were analyzed. The rate of non-compliance with medication was found to be 32.74% (55 out of 168). Logistic regression identified the educational level of parents (OR = 2.844, 95% CI: 2.182-3.214), monthly household income (OR = 1.945, 95% CI: 1.203-2.422), the number of medications taken (OR = 1.883, 95% CI: 1.314-2.201), and the level of epilepsy knowledge received (OR = 2.517, 95% CI: 1.852-3.009) as significant factors influencing non-compliance (all p < 0.05). A total score threshold of 6 was set for the predictive model. The area under the ROC curve was 0.713 (95% CI: 0.686-0.751), indicating the model's discriminative ability. CONCLUSIONS: The compliance to medication regimens among children with epilepsy is suboptimal and influenced by a multitude of factors. This study has developed a predictive model for medication compliance, which could serve as a valuable tool for clinical assessment and intervention planning regarding medication compliance in pediatric epilepsy patients.

Effects of epidural anesthesia and analgesia on the incidence of chronic pain after thoracoscopic lung surgery: A retrospective cohort study.

Objective: Chronic postoperative pain (CPSP) is common after thoracic surgery, even after the less invasive video-assisted thoracoscopic surgery (VATS). This study investigated the effect of thoracic epidural anesthesia (TEA) on the development of CPSP. Materials: We retrospectively analyzed the data of patients who underwent VATS at our center between 2020 and 2022. The enrolled patients were divided into the epidural block (EPI) and patient-controlled intravenous analgesia (PCIA) groups. A telephone questionnaire was used to collect information regarding CPSP, which was defined as a numerical rating scale (VAS) score ≥1 at 3 or 6 months postoperatively. Additionally, statistical analyses were performed to identify the risk factors for CPSP in the two groups. Results: Overall, 894 patients completed the follow-up interviews at 3 and 6 months, with 325 and 569 patients in the PCIA and EPI groups, respectively. The incidence rates of CPSP in the PCIA group at 3 and 6 months were 16.9 % (95 % confidence interval [CI]: 9.3-32.7 %) and 13.5 % (95 % CI: 8.7-33.4 %), and 10.3 % (95 % CI: 8.1-30.5 %) and 3.6 % (95 % CI: 3.5-21.5 %) in EPI group, respectively. The incidence of CPSP at 3 months (P = 0.0048) and 6 months (P < 0.005) was statistically significant in both groups. Age and lymph node dissection were significantly associated with CPSP. Conclusions: Compared to PCIA, TEA was associated with a lower incidence of CPSP after VATS, and should be considered an important part of the analgesia regimen for patients with VATS.

Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.

Kisspeptin receptor (KISS1R), belonging to the class A peptide-GPCR family, plays a key role in the regulation of reproductive physiology after stimulation by kisspeptin and is regarded as an attractive drug target for reproductive diseases. Here, we demonstrated that KISS1R can couple to the Gi/o pathway besides the well-known Gq/11 pathway. We further resolved the cryo-electron microscopy (cryo-EM) structure of KISS1R-Gq and KISS1R-Gi complexes bound to the synthetic agonist TAK448 and structure of KISS1R-Gq complex bound to the endogenous agonist KP54. The high-resolution structures provided clear insights into mechanism of KISS1R recognition by its ligand and can facilitate the design of targeted drugs with high affinity to improve treatment effects. Moreover, the structural and functional analyses indicated that conformational differences in the extracellular loops (ECLs), intracellular loops (ICLs) of the receptor, and the "wavy hook" of the Gα subunit may account for the specificity of G protein coupling for KISS1R signaling.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE Combined with Camrelizumab in Hepatocellular Carcinoma With Untreatable Progression After TACE Combined with Sorafenib Therapy: A Case Control Study.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. METHODS: The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. RESULTS: A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544). CONCLUSIONS: TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.

Combination of co-pyrolyzed biomass-sludge biochar and ultrasound for persulfate activation in antibiotic degradation: efficiency, synergistic effect, and reaction mechanism.

A carbon material Cu-corn straw-sludge biochar (Cu-CSBC) was prepared by hydrothermally modifying sewage sludge and corn stover. The composite coupled to ultrasound can effectively catalyze the activation of PS for organic pollutants degradation, and the removal rate of 20 mg/L TC reached 89.15% in 5 min in the presence of 0.5 g/L Cu-CSBC and 3 mM PS. The synergistic effect between the factors in the system, the reaction mechanism, and the efficient removal of TC in the aqueous environment were explored in a Cu-CSBC/US/PS system established for that purpose. Quenching experiments and electron paramagnetic resonance analysis both demonstrated the Cu-CSBC/US/PS system generated •OH, SO4-•, 1O2, and O2- •, which involved in the reaction. The Cu, carboxyl, and hydroxyl groups on the Cu-CSBC surface promoted the generation of radicals and non-radicals for the degradation process, which was dominated by both radical and non-radical pathways. The degradation pathway is proposed by measuring the intermediate products with LC-MS. Finally, the stability of the Cu-CSBC/US/PS system was tested under various reaction conditions. This study not only prepared a novel biochar composite material for the active degradation of organic pollutants by PS but also provided an effective method for the resource utilization of solid waste and sludge treatment.

Loss of Smek1 Induces Tauopathy and Triggers Neurodegeneration by Regulating Microtubule Stability.

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1-/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3ß (Gsk3ß) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner.

Preparation, characterization, antimicrobial evaluation, and grape preservation applications of polyvinyl alcohol/gelatin composite films containing zinc oxide@quaternized chitosan nanoparticles.

This study employed a precipitation method to synthesize zinc oxide@quaternised chitosan nanoparticles (ZnO@QAC NPs) containing different concentrations of zinc oxide, namely ZnO@QAC-2, ZnO@QAC-4, and ZnO@QAC-6. Subsequently, these nanoparticles were incorporated into matrices consisting of gelatine (Gn) and polyvinyl alcohol (PVA) separately, which were prepared by casting to form a biodegradable film. We assessed the physicochemical properties of ZnO@QAC NPs and physicochemical characteristics, antioxidant properties, antimicrobial activity and grape preservation efficacy of the film. Compared to the control group, the films showed a reduction in water vapor permeability by >9.38 %, an increase in tensile strength by over 51.95 %, over 70 % scavenging of ABTS free radicals, and good biocompatibility. Additionally, the antimicrobial activity of the films containing ZnO@QAC-6 increased by 37.6 %. In the grape preservation experiment, the weight loss of grapes wrapped in ZnO@QAC-2 film was reduced by 40.13 % on day 15 compared to unwrapped grapes. These results demonstrate that ZnO@QAC/PVA/Gn films have considerable potential for food packaging applications.

Coixol mitigates Toxoplasma gondii infection-induced liver injury by inhibiting the Toxoplasma gondii HSP70/TLR4/NF-κB signaling pathway in hepatic macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed, the dry mature seed kernel of the gramineous plant coix (Coix lacryma-jobi L. var. ma-yuen Stapf), is widely consumed as a traditional Chinese medicine and functional food in China and South Korea. We have previously demonstrated the protective effect of coixol, a polyphenolic compound extracted from coix, against Toxoplasma gondii (T. gondii) infection-induced lung injury. However, the protective effect of coixol on hepatic injury induced by T. gondii infection have not yet been elucidated. AIM OF THE STUDY: This study explores the impact of coixol on T. gondii infection-induced liver injury and elucidates the underlying molecular mechanisms. MATERIALS AND METHODS: Female BALB/c mice and Kupffer cells (KCs) were employed to establish an acute T. gondii infection model in vivo and an inflammation model in vitro. The study examined coixol's influence on the T. gondii-derived heat shock protein 70 (T.g.HSP70)/toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway in T. gondii-infected liver macrophages. Furthermore, a co-culture system of KCs and NCTC-1469 hepatocytes was developed to observe the impact of liver macrophages infected with T. gondii on hepatocyte injury. RESULTS: Coixol notably inhibited the proliferation of tachyzoites and the expression of T.g.HSP70 in mouse liver and KCs, and attenuated pathological liver injury. Moreover, coixol decreased the production of high mobility group box 1, tumor necrosis factor-α, and inducible nitric oxide synthase by suppressing the TLR4/NF-κB signaling pathway in vitro and in vivo. Coixol also mitigated KCs-mediated hepatocyte injury. CONCLUSIONS: Coixol protects against liver injury caused by T. gondii infection, potentially by diminishing hepatocyte injury through the suppression of the inflammatory cascade mediated by the T.g.HSP70/TLR4/NF-κB signaling pathway in KCs. These findings offer new perspectives for developing coixol as a lead compound for anti-T. gondii drugs.

Regulating the Grain-Growth Surface for Efficient Near-Infrared Perovskite Light-Emitting Diodes.

Metal halide perovskites hold great potential for next-generation light-emitting diodes (PeLEDs). Despite significant progress, achieving high-performance PeLEDs hinges on optimizing the interface between the perovskite crystal film and the charge transport layers, especially the buried interface, which serves as the starting point for perovskite growth. Here, we develop a bottom-up perovskite film modulation strategy using formamidine acetate (FAAc) to enhance the buried interface. This multifaceted approach facilitates the vertical-oriented growth of high-quality perovskites with minimized defects. Meanwhile, the in situ deprotonation between FA+ and ZnO could eliminate the hydroxyl (-OH) defects and modulate the energy level of ZnO. The resulting FAPbI3-PeLED exhibits a champion EQE of 23.84% with enhanced operational stability and suppressed EQE roll-off. This strategy is also successfully extended to other mixed-halide PeLEDs (e.g., Cs0.17FA0.83Pb(I0.75Br0.25)3), demonstrating its versatility as an efficient and straightforward method for enhancing the PeLEDs' performance.

Tertiary lymphoid structures as potential biomarkers for cancer prediction and prognosis.

Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregates formed in non-lymphoid tissues, including cancers, and are loci for the generation of in situ anti-tumor immune responses, which play a crucial role in cancer control. The state of TLS presence in cancer and its composition can significantly impact the treatment response and prognosis of patients. TLSs have the potential to serve as predictive and prognostic biomarkers for cancer. However, the mechanisms underlying TLS formation in cancer and how the essential components of TLSs affect cancer are not fully understood. In this review, we summarized TLS formation in cancer, the value of the TLS in different states of existence, and its key constituents for cancer prediction and prognosis. Finally, we discussed the impact of cancer treatment on TLSs.

Radiofrequency-responsive black phosphorus nanogel crosslinked with cisplatin for precise synergy in multi-modal tumor therapies.

Radiofrequency-responsive nanoparticles (RFNPs) have drawn increasingly attentions as RF energy absorbing antenna to enhance antitumor efficacy of radiofrequency ablation (RFA). However, it remains a huge challenge for inorganic RFNPs to precisely synergize RFA with other antitumor modes in a clinically acceptable way on bio-safety and bio-compatibility. In this work, RF-responsive black phosphorus (BP) nanogel (BP-Pt@PNA) was successfully fabricated by crosslinking coordination of cisplatin with BP and temperature sensitive polymer PNA. BP-Pt@PNA exhibited strong RF-heating effect and RF-induced pulsatile release of cisplatin. Under RF irradiation, BP-Pt@PNA exhibited cytotoxic enhancement on 4T1 cells. By the synergistic effect of BP and cisplatin, BP-Pt@PNA achieved RF-stimulated systemic immune effect, thus induced enhance suppression on tumor growth and metastasis. Moreover, BP-Pt@PNA realized long-term drug retention in tumor and favorable embolization to tumor-feeding arteries. With high drug loading capacity and favorable bio-safety and bio-degradability, BP-Pt@PNA is expected as an ideal RFNP for precisely synergizing RFA with other antitumor modes in clinical application.

Arctiin Mitigates Neuronal Injury by Modulating the P2X7R/NLPR3 Inflammasome Signaling Pathway.

Depression, recognized globally as a primary cause of disability, has its pathogenesis closely related to neuroinflammation and neuronal damage. Arctiin (ARC), the major bioactive component of Fructus arctii, has various pharmacological activities, such as anti-inflammatory and neuroprotective effects. Building on previous findings that highlighted ARC's capability to mitigate depression by dampening microglial hyperactivation and thereby reducing neuroinflammatory responses and cortical neuronal damage in mice, the current study delves deeper into ARC's therapeutic potential by examining its impact on hippocampal neuronal damage in depression. Utilizing both chronic unpredictable mild stress (CUMS)-induced depression model in mice and corticosterone (CORT)-stimulated PC12 cell model of neuronal damage, the techniques including Nissl staining, immunohistochemistry, western blotting, ELISA, lactate dehydrogenase assays, colony formation assays, immunofluorescence staining and molecular docking were employed to unravel the mechanisms behind ARC's neuroprotective effects. The findings revealed that ARC not only mitigates hippocampal neuropathological damage and reduces serum CORT levels in CUMS-exposed mice but also enhances cell activity while reducing lactate dehydrogenase release in CORT-stimulated PC12 cells. ARC attenuated neuroinflammatory responses and neuronal apoptosis by inhibiting the overactivation of the P2X7 receptor (P2X7R)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathway, similar to the effect of A438079 (P2X7R antagonist). Interestingly, pretreatment with A438079 blocked the neuroprotective effect of ARC. Computer modeling predicted that both ARC and A438079 have strong binding with P2X7R and they have the same binding site. These results suggested that ARC may exert a neuroprotective role by binding to P2X7R, thereby inhibiting the P2X7R/NLRP3 inflammasome signaling pathway.

Membrane electrolysis distillation for volatile fatty acids extraction from pH-neutral fermented wastewater.

Volatile fatty acids (VFAs) serve as building blocks for a wide range of chemicals, but it is difficult to extract VFAs from pH-neutral wastewater using evaporation methods because of the ionized form. This study presents a new membrane electrolysis distillation (MED) process that extracts VFAs from such fermentation solutions. MED uniquely integrates pH regulation and joule heating to facilitate the efficient evaporation of VFAs. This integration occurs alongside a hydrophobic membrane that ensures effective gas-liquid phase separation. Operating solely on electricity, MED achieved an acid flux rate of 12.03 g/m2/h at 6V. In contrast, the control results without the joule heating or pH swing only obtained a 0.23 g/m2/h and 0.32 g/m2/h flux, respectively. In addition, a physicochemical model was developed to assess the impacts of temperature on membrane surface pH. This system enhances resource recovery from waste streams and helps achieve a circular carbon economy.

Golgi Protein 73 Promotes Angiogenesis in Hepatocellular Carcinoma.

Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.

Mature tertiary lymphoid structures: important contributors to anti-tumor immune efficacy.

Tertiary lymphoid structures (TLS) represent the ectopic aggregations of immune cells arising during chronic inflammation or tumor progression. In cancer, TLS are often associated with beneficial clinical outcomes in patients undergoing immunotherapy, underscoring their prognostic and predictive significance. Mature TLS, characterized by germinal centers and areas of T-cell and B-cell aggregation, are considered primary locations for activating and maintaining both humoral and cellular anti-tumor immune effects. Despite their recognized importance, the mechanisms driving the formation of mature TLS in cancer and their influence on the immune response within tumors remain insufficiently understood. Therefore, this review aims to comprehensively explore the structural composition, development mechanisms, maturity impact factors, immunological function, and innovative therapeutic strategies of mature TLS within the tumor microenvironment. The research summarized herein offers novel insights and considerations for therapeutic approaches to promote TLS generation and maturation in patients with cancer, representing a promising avenue for future cancer therapies.

Type 2 diabetes microenvironment promotes the development of Parkinson's disease by activating microglial cell inflammation.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, and type 2 diabetes (T2DM) and PD are influenced by common genetic and environmental factors. Mitochondrial dysfunction and inflammation are common pathogenic mechanisms of both diseases. However, the close association between PD and T2DM and the specific relationship between them are not yet clear. This study aimed to reveal the specific connection between the two diseases by establishing a mouse model of comorbid PD and T2DM, as well as a Bv2 cell model. Methods: C57BL/6 mouse were used to construct a model of PD with T2DM using streptozotocin and rotenone, while Bv2 cells were used to simulate the microenvironment of PD and T2DM using rotenone and palmitate. Behavioral tests were conducted to assess any differences in motor and cognitive functions in mouse. Immunohistochemistry was used to analyze the number of dopaminergic neurons in the substantia nigra region of mouse. Western blotting was used to detect the expression levels of TH, P-NFκB, NFκB, Cyclic GMP-AMP synthase (cGAS), and Stimulator of interferon genes (STING) proteins in the substantia nigra region of mouse and Bv2 cells. qRT-PCR was used to analyze the expression levels of IL1ß, IL6, and TNF-α. Seahorse technology was used to assess mitochondrial function in Bv2 cells. Results: T2DM exacerbated the motor and cognitive symptoms in mouse with PD. This effect may be mediated by disrupting mitochondrial function in microglial cells, leading to damaged mtDNA leakage into the cytoplasm, subsequently activating the cGAS-STING pathway and downstream P-NFκB/NFκB proteins, triggering an inflammatory response in microglial cells. Microglial cells release inflammatory factors such as IL1ß, IL6, and TNF-α, exacerbating neuronal damage caused by PD. Conclusion: Our study results suggest that T2DM may exacerbate the progression of PD by damaging mitochondrial function, and activating microglial cell inflammation. The detrimental effects on Parkinson's disease may be achieved through the activating of the cGAS-STING protein pathway.