A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress.

Mitochondria play essential roles in cancer cell adaptation to hypoxia, but the underlying mechanisms remain elusive. Through mitochondrial proteomic profiling, we here find that the prolyl hydroxylase EglN1 (PHD2) accumulates on mitochondria under hypoxia. EglN1 substrate-binding region in the ß2ß3 loop is responsible for its mitochondrial translocation and contributes to breast tumor growth. Furthermore, we identify AMP-activated protein kinase alpha (AMPKα) as an EglN1 substrate on mitochondria. The EglN1-AMPKα interaction is essential for their mutual mitochondrial translocation. After EglN1 prolyl-hydroxylates AMPKα under normoxia, they rapidly dissociate following prolyl-hydroxylation, leading to their immediate release from mitochondria. In contrast, hypoxia results in constant EglN1-AMPKα interaction and their accumulation on mitochondria, leading to the formation of a Ca2+ /calmodulin-dependent protein kinase 2 (CaMKK2)-EglN1-AMPKα complex to activate AMPKα phosphorylation, ensuring metabolic homeostasis and breast tumor growth. Our findings identify EglN1 as an oxygen-sensitive metabolic checkpoint signaling hypoxic stress to mitochondria through its ß2ß3 loop region, suggesting a potential therapeutic target for breast cancer.

High-Index Faceted Cu2 O@CuO Mesocrystals Act as Efficient Catalyst for Si Hydrochlorination to Trichlorosilane.

Mesocrystals (MCs) with high-index facets may have superior catalytic properties to those with low-index facets and their nanocrystal counterparts. However, synthesizing such mesocrystal materials is still very challenging because of the metastability of MCs and energetic high-index crystal facets. This work reports a successful solvothermal method followed by calcination for synthesizing copper oxide-based MCs possessing a core-shell structure (denoted as Cu2 O@CuO HIMCs). Furthermore, these MCs are predominantly bounded by the high-index facets such as {311} or {312} with a high-density of stepped atoms. When used as catalysts in Si hydrochlorination to produce trichlorosilane (TCS, the primary feedstock of high-purity crystalline Si), Cu2 O@CuO HIMCs exhibit significantly enhanced Si conversion and TCS selectivity compared to those with flat surfaces and their nanostructured counterparts. Theoretical calculations reveal that both the core-shell structure and the high-index surface contribute to the increased electron density of Cu sites in Cu2 O@CuO HIMCs, promoting the adsorption and dissociation of HCl and stabilizing the dissociated Cl* intermediate. This work provides a simple method for synthesizing high-index faceted MCs and offers a feasible strategy to enhance the catalytic performance of MCs.

Single-Atom Ru Alloyed with Ni Nanoparticles Boosts CO2 Methanation.

Designing catalysts to proceed with catalytic reactions along the desired reaction pathways, e.g., CO2 methanation, has received much attention but remains a huge challenge. This work reports one Ru1Ni single-atom alloy (SAA) catalyst (Ru1Ni/SiO2) prepared via a galvanic replacement reaction between RuCl3 and Ni nanoparticles (NPs) derived from the reduction of Ni phyllosilicate (Ni-ph). Ru1Ni/SiO2 achieved much improved selectivity toward hydrogenation of CO2 to CH4 and catalytic activity (Turnover frequency (TOF) value: 40.00 × 10-3 s-1), much higher than those of Ni/SiO2 (TOF value: 4.40 × 10-3 s-1) and most reported Ni-based catalysts (TOF value: 1.03 × 10-3-11.00 × 10-3 s-1). Experimental studies verify that Ru single atoms are anchored onto the Ni NPs surface via the Ru1-Ni coordination accompanied by electron transfer from Ru1 to Ni. Both in situ experiments and theoretical calculations confirm that the interface sites of Ru1Ni-SAA are the intrinsic active sites, which promote the direct dissociation of CO2 and lower the energy barrier for the hydrogenation of CO* intermediate, thereby directing and enhancing the CO2 hydrogenation to CH4.

Isolating Single Sn Atoms in CuO Mesocrystal to Form Ordered Atomic Interfaces: An Effective Strategy for Designing Highly Efficient Mesocrystal Catalysts.

Tuning the electronic structures of mesocrystals at the atomic level is an effective approach to obtaining unprecedented properties. Here, a lattice-confined strategy to obtain isolated single-site Sn atoms in CuO mesocrystals to improve catalytic performance is reported. The Sn/CuO mesocrystal composite (Sn/CuO MC) has ordered Sn-O-Cu atomic interfaces originated from the long-range ordering of the CuO mesocrystal itself. X-ray absorption fine structure measurements confirm that the positively charged Sn atoms can tune the electronic structure of the Cu atoms to some extent in Sn/CuO MC, quite different from that in the conventional single-atom Sn-modified CuO nanoparticles and nanoparticulate SnO2 -modified CuO mesocrystal catalysts. When tested for the Si hydrochlorination reaction to produce trichlorosilane, Sn/CuO MC exhibits significantly better performances than the above two catalysts. Theoretical calculations further reveal the electronic modification to the active Cu component and the induced improvement in HCl adsorption, and thus enhance the catalytic performance. This work demonstrates how to design efficient metal oxide mesocrystal catalysts through an electronic structure modification approach.

Public Health Concern on Sedentary Behavior and Cardiovascular Disease: A Bibliometric Analysis of Literature from 1990 to 2022.

Background and Objectives: Cardiovascular disease is a long-term threat to global public health security, while sedentary behavior is a modifiable behavior among cardiovascular risk factors. This study aimed to analyze the peer-reviewed literature published globally on sedentary behavior and cardiovascular disease (SB-CVD) and identify the hotspots and frontiers within this research area. Materials and Methods: Publications on SB-CVD from 1990 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were applied to perform bibliometric and knowledge mapping visualization analyses. Results: A total of 2071 publications were retrieved, presenting a gradual growing trend. Authors from the USA topped the list with 748 (36.12%), followed by authors from England (373, 18.01%) and Australia (354, 17.09%). The University of Queensland, Australia, led with 95 (4.5%) publications. The top five active authors were all from Australia, while Dunstan D and Owen N published the most documents (56, 2.7%). A total of 71.27% of the publications received funding, and the United States Department of Health and Human Services provided 363 (17.53%) grants. Public Environmental Occupational Health (498, 24.05%), Sport Sciences (237, 11.44%), and Cardiac Cardiovascular Systems (212, 10.24%) were the three most popular disciplines, while PLOS One (96, 4.64%) and BMC Public Health (88, 4.25%) were the two most popular journals. Investigations within the SB-CVD research area addressed the entire lifespan, the most popular type of research was the epidemiological study, and the accelerometer was the primary instrument for measuring sedentary behavior. In terms of variables, physical activity and sedentary behavior were the dominant lifestyle behaviors, while obesity and hypertension were common health problems. Occupational physical activity and guidelines are at the frontier and are currently in the burst stage. Conclusions: The last three decades have witnessed the rapid development of the SB-CVD research area, and this study provided further research ideas for subsequent investigations.

Structural Design and Synthesis of an SnO2 @C@Co-NC Composite as a High-Performance Anode Material for Lithium-Ion Batteries.

To overcome the drawbacks of the structural instability and poor conductivity of SnO2 -based anode materials, a hollow core-shell-structured SnO2 @C@Co-NC (NC=N-doped carbon) composite was designed and synthesized by employing the heteroatom-doping and multiconfinement strategies. This composite material showed a much-reduced resistance to charge transfer and excellent cycling performance compared to the bare SnO2 nanoparticles and SnO2 @C composites. The doped heteroatoms and heterostructure boost the charge transfer, and the porous structure shortens the Li-ion diffusion pathway. Also, the volume expansion of SnO2 NPs is accommodated by the hollow space and restricted by the multishell heteroatom-doped carbon framework. As a result, this structured anode material delivered a high initial capacity of 1559.1 mA h g-1 at 50 mA g-1 and an initial charge capacity of 627.2 mA h g-1 at 500 mA g-1 . Moreover, the discharge capacity could be maintained at 410.8 mA h g-1 after 500 cycles with an attenuation rate of only 0.069 % per cycle. This multiconfined SnO2 @C@Co-NC structure with superior energy density and durable lifespan is highly promising for the next-generation lithium-ion batteries.

Clinical characteristics and surgical treatment of haemophilic pseudotumor: A retrospective analysis of thirty-four patients.

AIMS: Haemophilic pseudotumor (HPT) is a rare but challenging complication of haemophilia. This study was intended to provide our experience about clinical characteristics and surgical treatment of HPT. METHODS: Clinical medical records were retrieved from the Hemophilia Center, Nanfang Hospital, to identify the patients who had been surgically treated from 1 January 2006 to 31 December 2017 with a definite diagnosis of HPT. Their clinical features, surgical management, outcomes and complications after surgery were analysed. RESULTS: We identified 34 patients with HPT who had surgical treatment over a 12-year period and five of them had multiple HPTs. The incidence of HPT at this centre was 2.3% over the dozen years. A previous trauma leading to the development of HPT was reported in 18 cases (52.9%). The HPT affected only soft tissue in 7 patients, bone and soft tissue in 25 ones and joint in 2 ones. Preoperative infection and fistula formation happened in ten patients, two of whom were related to abdominal HPTs. Enterococcus faecalis was cultured in five cases with fistula formation. HPT associated with pathological fracture was observed in five cases, two of whom were treated by external fixation and 3 by HPT resection and metallic internal fixation. Amputation was performed for nine patients, 6 of whom had preoperative infection and fistula formation. Their follow-up duration averaged 4.2 ± 2.9 years (range, from 1 to 13.5 years) after surgery. Of all our cases, three suffered from postoperative infection, five from recurrence of HPT and two with external fixation from fracture non-union. CONCLUSIONS: HPT patients with preoperative infection had worse prognosis than those without. Surgical treatment plus intensive replacement therapy was effective for HPT but with a high rate of complications. HPT resection and metallic internal fixation rather than external fixation should be recommended for HPT patients with pathological fracture.

Clinical Characteristics and Distribution of Thumb Polydactyly in South China: A Retrospective Analysis of 483 Hands.

PURPOSE: This study was intended to characterize the epidemiological features of thumb polydactyly (TP) in South China. METHODS: Clinical records were retrieved from 1 central hospital in South China to identify the patients with a definite diagnosis of TP from January 2004 to January 2017. The cases were classified by their x-ray appearance. The data collected included sex, age at first operation, reoperation, family history, unilateral/bilateral polydactyly, right/left hand involvement in unilateral cases, classification of polydactyly, and the presence of associated congenital anomalies. RESULTS: A total of 428 patients with a definite diagnosis of TP were identified (278 males and 150 females) involving 483 cases, 373 unilateral and 55 bilateral. A syndrome or associated congenital anomaly was found in 26 (18 unilateral and 8 bilateral cases). A dominant thumb, larger and more developed, was observed in 448 hands (93%), and was the ulnar thumb in 433. Owing to postoperative complications, 31 thumbs (6.4%) underwent reoperation. The average interval from initial surgery to reoperation was 4.8 years. CONCLUSIONS: Thumb polydactyly had a male predominance in this Chinese cohort, mostly occurring on the right hand with an ulnar dominant thumb. Bilateral cases had a higher incidence of associated anomaly and positive family history than unilateral cases. The need for additional surgery for TP might occur as late as 4.8 years after primary surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Subdivision of injured area for Schatzker IV tibial plateau fracture repair: A report of 12 cases.

BACKGROUND: Treatment of Schatzker IV tibial plateau fractures is challenging due to the wide variety of potential fracture morphologies and injury to multiple ligaments. Subdivision of the injured area into three zones may simplify the preoperative plan. In this study, we reported 12 cases of Schatzker IV tibial plateau fracture that were treated with pre-operative plans based on a new subdivision of the injured area. METHODS: From January 2012 to April 2016, 12 patients with a Schatzker IV tibial plateau fracture were treated in our hospital with preoperative plans guided by the new sub-division method. Clinical and radiological results were evaluated during follow-up. RESULTS: In all cases, the incisions healed without skin necrosis, and the average Lysholm knee score was 73 points (range, 53-90) at the final follow-up. CONCLUSION: Sub-division of the injured area represented a useful strategy for preoperative surgical planning in the treatment of Schatzker IV tibial plateau fractures.

One-dimensional fossil-like γ-Fe2O3@carbon nanostructure: preparation, structural characterization and application as adsorbent for fast and selective recovery of gold ions from aqueous solution.

One-dimensional (1D) magnetic nanostructures with high thermal stability have important industrial applications, but their fabrication remains a big challenge. Herein we demonstrate a scalable approach for the preparation of stable 1D γ-Fe2O3@carbon, which is also applicable for other metal oxide-core and carbon-shell nanostructures, such as 1D TiO2@carbon. One-dimensional ferric oxyhydroxide (α-FeO(OH)) was initially prepared by a hydrothermal method, followed by carbon coating through hydrothermal treatment of the resulting metal oxide in glucose solution. After calcination in N2 gas at 500 °C and subsequent exposure to air, the initial carbon-coated 1D α-Fe2O3 was converted to 1D γ-Fe2O3@carbon, which was very stable without any observed changes even after 1.5 years of storage under ambient conditions. The materials were then used as adsorbents and found to be highly selective towards Au (III) adsorption, of which the maximum adsorption capacity is about 600 mg Au/g sorbent (1132 mg Au/g carbon). The spent sorbent containing Au after adsorption can be readily collected by applying a magnetic field due to the presence of the magnetic core, and the adsorbed Au particles are subsequently recovered after the combustion and dissolution of the sorbent. This work demonstrates not only a facile approach to the fabrication of robust 1D magnetic materials with a stable carbon shell, but also a possible cyanide-free process for the fast and selective recovery of gold from electronic waste and industrial water.

The sonochemical approach improves the CuO-ZnO/TiO(2) catalyst for WGS reaction.

The CuO-ZnO composite was deposited onto two kinds of titania supports, which are synthetic mesoporous TiO2 and commercial TiO2 P25 (Degussa), via the ultrasound assisted precipitation and incipient wetness impregnation (IWI) methods, respectively. The catalysts were tested for WGS reaction in the temperature range of 200-400 °C, and the best catalytic performance was achieved for the sonochemically prepared catalysts supported on the commercial TiO2 P25, which contains well crystallized anatase and rutile phases. Although the synthetic mesoporous TiO2 has a higher surface area, its textural structure is not stable under the reaction conditions, leading to gradual deactivation of the CuO-ZnO/TiO2 catalyst. It is found that the sonochemical preparation offers at least two advantages: (1) generation of mesopores on the catalyst surface and (2) doping of ZnO into the CuO phase. The doping of ZnO, particularly in the case of commercial TiO2 P25, provides high activity and extra stability to the active phase of Cu(0). These new findings provide new insights into the design and development of better heterogeneous catalysts for WGS reaction.

Scalable synthesis of interconnected porous silicon/carbon composites by the Rochow reaction as high-performance anodes of lithium ion batteries.

Despite the promising application of porous Si-based anodes in future Li ion batteries, the large-scale synthesis of these materials is still a great challenge. A scalable synthesis of porous Si materials is presented by the Rochow reaction, which is commonly used to produce organosilane monomers for synthesizing organosilane products in chemical industry. Commercial Si microparticles reacted with gas CH3 Cl over various Cu-based catalyst particles to substantially create macropores within the unreacted Si accompanying with carbon deposition to generate porous Si/C composites. Taking advantage of the interconnected porous structure and conductive carbon-coated layer after simple post treatment, these composites as anodes exhibit high reversible capacity and long cycle life. It is expected that by integrating the organosilane synthesis process and controlling reaction conditions, the manufacture of porous Si-based anodes on an industrial scale is highly possible.

Posterior Wall Fragments in Acetabular Both-Column Fractures: Morphology, Type, and the Significance of its Projection.

OBJECTIVE: Most both-column acetabular fractures are combined with posterior wall fragments. However, the morphology of this posterior wall is varied, and how to fix this posterior wall remains a controversial topic. To investigate the morphological characteristics of posterior wall fragments of both-column acetabular fractures and select corresponding fixation methods. METHODS: Data from 352 patients with acetabular fractures admitted to the level one trauma centre in our hospital between January 2006 and December 2022 were collected. The morphology of posterior wall fragments was observed and analyzed in 83 cases of both-column acetabular fractures and classified according to the consistency of posterior wall morphology. A fracture map of the posterior wall was created on a normal template according to the three morphological types of posterior wall fragments. Finally, the high-incidence area of the posterior wall fracture was projected onto the iliac fossa and the medial side of the posterior column to guide the fixation of the posterior wall fragment using the anterior intrapelvic approach. RESULTS: Fractures were divided into four types: I, large posterior wall fragment which was high in the ilium bone (34 cases, 41.0%); II, posterior wall fragment in the acetabular parietal region (18 cases, 21.7%); III, posterior wall marginal fracture (10 cases, 12.0%); and IV, non-combined posterior wall fracture (21 cases, 25.3%). The most common morphologies of the posterior wall fragments of the first two types were mapped and projected onto the anterior iliac inner plate and medial side of the posterior column, where the corresponding area could be used to guide the insertion of the internal fixation. CONCLUSION: Both-column acetabular fractures combined with posterior wall fractures can be divided into four types according to the morphology of the posterior wall fragment. Understanding the corresponding three-dimensional morphology and projection position of different types of these fragments can help surgeons determine the position and orientation of internal fixation of posterior wall fractures.

Artificial intelligence for optimizing recruitment and retention in clinical trials: a scoping review.

OBJECTIVE: The objective of our research is to conduct a comprehensive review that aims to systematically map, describe, and summarize the current utilization of artificial intelligence (AI) in the recruitment and retention of participants in clinical trials. MATERIALS AND METHODS: A comprehensive electronic search was conducted using the search strategy developed by the authors. The search encompassed research published in English, without any time limitations, which utilizes AI in the recruitment process of clinical trials. Data extraction was performed using a data charting table, which included publication details, study design, and specific outcomes/results. RESULTS: The search yielded 5731 articles, of which 51 were included. All the studies were designed specifically for optimizing recruitment in clinical trials and were published between 2004 and 2023. Oncology was the most covered clinical area. Applying AI to recruitment in clinical trials has demonstrated several positive outcomes, such as increasing efficiency, cost savings, improving recruitment, accuracy, patient satisfaction, and creating user-friendly interfaces. It also raises various technical and ethical issues, such as limited quantity and quality of sample size, privacy, data security, transparency, discrimination, and selection bias. DISCUSSION AND CONCLUSION: While AI holds promise for optimizing recruitment in clinical trials, its effectiveness requires further validation. Future research should focus on using valid and standardized outcome measures, methodologically improving the rigor of the research carried out.

Effect of scapular stabilization exercises on subacromial pain (impingement) syndrome: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the effectiveness of scapular stabilization exercises (SSE) in the treatment of subacromial pain syndrome (SAPS). Methods: Clinical randomized controlled trials (RCTs) on SSE in the treatment of SAPS were searched electronically in PubMed, Science Direct, Cochrane Central Register of Controlled Trials (CENTRAL), EBSCOhost, Physiotherapy Evidence Database (PEDro), Web of Science, and other databases from 2000 to 2022, supplemented by manual search. Final RCTs were selected based on inclusion and exclusion criteria, and the Physiotherapy Evidence Database scale was used to evaluate the methodological quality of the study. A meta-analysis was conducted on data using the RevMan5.4 software. Results: Eight RCTs involving 387 participants were included. The meta-analysis showed that the experimental group (SSE) had greater improvements in the Visual Analog Scale score [Weighted Mean Difference (WMD) = -0.94, 95% CI (-1.23, -0.65), p < 0.001] and the Shoulder Pain and Disability Index score [WMD = -10.10, 95% CI (-18.87, -1.33), p = 0.02] than the control group (conventional physical therapy). However, range of motion (ROM) was not found to be greater in the experimental group than in the control group. Conclusion: Existing evidence moderately supports the efficacy of SSE for reducing pain and improving function in SAPS, without significant improvement in ROM. Future research should focus on larger, high-quality, standardized protocols to better understand SSE's effects across diverse SAPS populations, treatment, and outcome measures. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=307437, CRD42022307437.

Porous In2O3 Hollow Tube Infused with g-C3N4 for CO2 Photocatalytic Reduction.

Converting CO2 into energy-rich fuels by using solar energy is a sustainable solution that promotes a carbon-neutral economy and mitigates our reliance on fossil fuels. However, affordable and efficient CO2 conversion remains an ongoing challenge. Here, we introduce polymeric g-C3N4 into the pores of a hollow In2O3 microtube. This architecture results in a compact and staggered arrangement between g-C3N4 and In2O3 components with an increased contact interface for improved charge separation. The hollow interior further contributes to strengthening light absorption. The resulting g-C3N4-In2O3 hollow tubes exhibit superior activity (274 µmol·g-1·h-1) toward CO2 to CO conversion in comparison with those of pure In2O3 and g-C3N4 (5.5 and 93.6 µmol·g-1·h-1, respectively), underlining the role of integrating g-C3N4 and In2O3 in this advanced system. This work offers a strategy for the advanced design and preparation of hollow heterostructures for optimizing CO2 adsorption and conversion by integrating inorganic and organic semiconductors.

Glycolysis and tumor progression promoted by the m6A writer VIRMA via m6A-dependent upregulation of STRA6 in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, highlighting the urgent need to elucidate the underlying oncogenic mechanisms. VIRMA is a classic isoform of methyltransferases that participates in epigenetic transcriptomic modification in eukaryotic mRNAs. However, the exact roles of VIRMA in PDAC remain unclear. Here, we identified that VIRMA is highly expressed in PDAC, and histone modifications of the promoter may partly account for this dysregulation. Moreover, VIRMA is closely related to glycolysis and poor prognosis in PDAC. We further determined that STRA6 is a direct downstream target of VIRMA in PDAC by RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq). VIRMA is involved in gene expression regulation via 3' UTR targeting of STRA6 mRNA. Furthermore, the m6A reader IGF2BP2 was shown to critically contribute to the stability of STRA6 mRNA. We describe the role of VIRMA in promoting signaling via the STRA6/STAT3 axis, which results in increased levels of HIF-1α, a key activator of glycolysis. In vivo and in vitro experiments reveal that the VIRMA-STRA6-STAT3-HIF-1α axis plays an instrumental role in glycolysis and tumor progression in PDAC. In conclusion, we demonstrate that VIRMA can increase glycolysis in PDAC by upregulating STRA6, a cell surface membrane protein that stimulates the STAT3 pathway, thereby activating HIF-1α and leading to pancreatic cancer malignancy. Overall, our data strongly suggest that the VIRMA-STRA6-STAT3-HIF-1α axis is a viable therapeutic target in PDAC.

Association Between Serum Zinc and Non-Alcoholic Fatty Liver Disease and Advanced Liver Fibrosis: NHANES 2011-2016.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Tumor-associated macrophages drive glycolysis through the IL-8/STAT3/GLUT3 signaling pathway in pancreatic cancer progression.

Glycolytic metabolism is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and tumor-associated stromal cells play important roles in tumor metabolism. We previously reported that tumor-associated macrophages (TAMs) facilitate PDAC progression. However, little is known about whether TAMs are involved in regulating glycolysis in PDAC. Here, we found a positive correlation between CD68+ TAM infiltration and FDG maximal standardized uptake (FDG SUVmax) on PET-CT images of PDAC. We discovered that the glycolytic gene set was prominently enriched in the high TAM infiltration group through Gene Set Enrichment Analysis using The Cancer Genome Atlas database. Mechanistically, TAMs secreted IL-8 to promote GLUT3 expression in PDAC cells, enhancing tumor glycolysis both in vitro and in vivo, whereas this effect could be blocked by the IL-8 receptor inhibitor reparixin. Furthermore, IL-8 promoted the translocation of phosphorylated STAT3 into the nucleus to activate the GLUT3 promoter. Overall, we demonstrated that TAMs boosted PDAC cell glycolysis through the IL-8/STAT3/GLUT3 signaling pathway. Our cumulative findings suggest that the abrogation of TAM-induced tumor glycolysis by reparixin might exhibit an antitumor impact and offer a potential therapeutic target for PDAC.

Extracellular vesicle-packaged lncRNA from cancer-associated fibroblasts promotes immune evasion by downregulating HLA-A in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.