Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis.

Lysine lactylation (Kla), an epigenetic mark triggered by lactate during glycolysis, including the Warburg effect, bridges metabolism and gene regulation. Enzymes such as p300 and HDAC1/3 have been pivotal in deciphering the regulatory dynamics of Kla, though questions about additional regulatory enzymes, their specific Kla substrates, and the underlying functional mechanisms persist. Here, we identify SIRT1 and SIRT3 as key "erasers" of Kla, shedding light on their selective regulation of both histone and non-histone proteins. Proteomic analysis in SIRT1/SIRT3 knockout HepG2 cells reveals distinct substrate specificities toward Kla, highlighting their unique roles in cellular signaling. Notably, we highlight the role of specific Kla modifications, such as those on the M2 splice isoform of pyruvate kinase (PKM2), in modulating metabolic pathways and cell proliferation, thereby expanding Kla's recognized functions beyond epigenetics. Therefore, this study deepens our understanding of Kla's functional mechanisms and broadens its biological significance.

A carbon/oxygen calculation method to improve the response sensitivity of carbon/oxygen logging.

Carbon/Oxygen logging is an effective method to perform oil layer recognition and oil saturation calculation, which plays an important role in the evaluation of remaining oil after casing. At present, there are two main methods to calculate the ratio of carbon to oxygen (C/O). Compared with the energy window count method, the element yield method can avoid the influence of background count in the gamma spectrum and calculated carbon/oxygen value has the higher sensitivity and better accuracy, but it is still greatly affected by carbon and oxygen elements in the formation skeleton. Therefore, a new carbon/oxygen calculation method is proposed in this paper to overcome the influence of formation skeleton and improve the response sensitivity of Carbon/Oxygen logging. Based on Monte Carlo method, the inelastic gamma spectrum of pure sandstone and pure limestone skeletons are obtained. Based on spectrum analysis technology, the ratio relationship of carbon, oxygen yield and skeleton mark element (Si, Ca) yield in two skeletons are obtained. Using these ratio relationships, the carbon and oxygen yields from the sandstone and limestone reservoir skeletons are deducted from the total carbon and oxygen yield. A new carbon/oxygen parameter called the residual carbon/oxygen value (C/O)R is calculated to perform oil-water recognition and a set of oil saturation calculation model suitable for the residual carbon/oxygen value is proposed. The environment application of the residual carbon/oxygen value is also analyzed. The study shows that the residual carbon/oxygen value has higher sensitivity than original carbon/oxygen value in oil layer recognition and has a great accuracy in oil saturation calculation. In environment application aspect, the residual carbon/oxygen value is basically unaffected by formation water salinity and is affected by wellbore fluid and wellbore size obviously. This new carbon/oxygen value calculation method has an important significance to improve the application effect of Carbon/Oxygen logging.

Clinical outcomes of unicompartmental knee arthroplasty and total knee arthroplasty in the same patient.

BACKGROUND: Osteoarthritis has become the predominant manifestation of arthritic conditions on a worldwide scale and serves as a significant instigator of pain, impairment, and increasing socio-economic strain on a global level. The ongoing discourse on the choice between total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) for patients suffering from anterior medial osteoarthritis continues to ignite scholarly controversy. Our objective was to assess and compare the clinical outcomes of UKA and TKA within the same patient, hereby offering a novel perspective on this topic. MATERIALS AND METHODS: Fifty-seven individuals who underwent TKA on one knee and UKA on the other knee at the Department of Orthopaedics, First Hospital of Hebei Medical University between March 2019 and March 2024 were analysed for this retrospective study. We conducted a comprehensive examination and evaluation of perioperative laboratory assessments, radiological examinations, knee functionality, contentment levels, and postoperative complications within the two groups. RESULTS: Following surgical procedures, levels of hemoglobin, red blood cells, and albumin were found to be elevated in the UKA group when compared to the TKA group (hemoglobin: 121.2 ± 12.54 vs. 110.1 ± 13.21 g/L; red blood cells: 4.0 ± 0.47 vs. 3.6 ± 0.42 *1012/L; albumin: 37.7 ± 5.66 vs. 35.3 ± 5.23 g/L). There is a significant difference in the hip-knee-ankle angles between the postoperative UKA group and the TKA group (5.3 ± 3.46° vs. 4.1 ± 2.86°, p < 0.05). There existed no notable disparity in postoperative visual analog scale, knee society score, and forgotten joint score between the two groups. However, a remarkable variance was observed in postoperative range of motion between the two groups (116.4 ± 5.96° vs. 108.4 ± 5.32°). CONCLUSION: We found that UKA resulted in less physical strain, less postoperative inflammatory response, improved joint mobility, although with less effective lower limb force line correction compared to TKA. Many patients have shown a preference for UKA and express higher levels of satisfaction with the procedure.

Trends and challenges on inflammatory microenvironment in diabetic wound from 2014 to 2023: A bibliometric analysis.

The disturbance of the inflammatory microenvironment is a frequent pathological trait of diabetic wounds, contributing to the emergence of numerous chronic illnesses. This is crucial in both the development and recovery of wounds caused by diabetes. This study aims to perform a bibliometric analysis of research on the inflammatory microenvironment within the domain of diabetic wounds (DW) over the past 10 years. The objective is to map out the current global research landscape, pinpoint the most significant areas of study and offer guidance for future research avenues. Our research involved querying the Web of Science Core Collection (WoSCC) database for all pertinent studies on the inflammatory microenvironment in diabetic wounds (DW). We utilized bibliometric tools such as CiteSpace, VOSviewer and R (version 4.3.1) to identify and highlight the most impactful studies in the field. The study encompassed a review of 1454 articles published from 2014 to 2023, highlighting China and the United States as pivotal nations in the research of the inflammatory microenvironment in diabetic wounds (DW). Within this sphere, the University of Michigan and Harvard University in the United States, along with Shanghai Jiaotong University in China, emerged as the most prolific institutions. WANG Y from China was identified as the most productive author, while KUNKEL SL from the United States received the most citations. The research primarily focuses on topics such as wound healing, repair processes, angiogenesis, oxidative stress and macrophage activity. Additionally, "macrophage" and "delivery" were pinpointed as the leading subjects with promising research potential in this area. Research on the inflammatory microenvironment of diabetic wounds is rapidly advancing through active international collaboration. The study of new mechanisms related to the inflammatory microenvironment and the development of novel materials for repair based on this microenvironment represent emerging fields of future research, particularly in terms of translational applications. This may offer guidance and novel perspectives for further research in the area of the diabetic wound inflammatory microenvironment.

Non-surgical vs. surgical treatment of distal radius fractures: a meta-analysis of randomized controlled trials.

PURPOSE: To compare the clinical outcomes between nonsurgical and surgical treatment of distal radius fracture. METHODS: We performed a systematic literature search by using multiple databases, including Medline, PubMed, and Cochrane. All databases were searched from the earliest records through February 2023. The study compared nonsurgical versus surgical treatment of distal radius fractures and included only randomized controlled trials (RCTS). RESULTS: There were seventeen randomized controlled trials retrieved. A total of 1730 patients were included: 862 in the nonsurgical group and 868 in the surgical group. The results showed a significant reduction in DASH score with surgical treatment (WMD 3.98, 95% CI (2.00, 5.95), P < 0.001). And in grip strength (%), the results showed a significant improvement in surgical treatment compared with non-surgical treatment (WMD - 6.60, 95% CI (-11.61, -1.60), P = 0.01). There was significant difference in radial inclination, radial length, volar title, range of wrist pronation, range of wrist supination. However, no difference in radial deviation, ulnar deviation, ulnar variance, range of wrist extension and range of wrist flexion was observed. CONCLUSIONS: The results of this meta-analysis suggest that some patients with surgical treatment of distal radius fractures not only improved the grip strength (%), decreased the DASH score, but also improved the range of wrist pronation and the range of wrist supination compared with nonsurgical treatment. Based on the present meta-analysis, we suggest that some patients with surgical treatment might be more effective in patients with distal radius fracture.

Quantitative Proteomics Reveal the Role of Matrine in Regulating Lipid Metabolism.

Hyperlipidemia (HLP) is a prevalent systemic metabolic disorder characterized by disrupted lipid metabolism. Statin drugs have long been the primary choice for managing lipid levels, but intolerance issues have prompted the search for alternative treatments. Matrine, a compound derived from the traditional Chinese medicine Kushen, exhibits anti-inflammatory and lipid-lowering properties. Nevertheless, the mechanism by which matrine modulates lipid metabolism remains poorly understood. Here, we investigated the molecular mechanisms underlying matrine's regulation of lipid metabolism. Employing quantitative proteomics, we discovered that matrine increases the expression of LDL receptor (LDLR) in HepG2 and A549 cells, with subsequent experiments validating its role in enhancing LDL uptake. Notably, in hyperlipidemic hamsters, matrine effectively lowered lipid levels without affecting body weight, which highlights LDLR as a critical target for matrine's impact on HLP. Moreover, matrine's potential inhibitory effects on tumor cell LDL uptake hint at broader applications in cancer research. Additionally, thermal proteome profiling analysis identified lipid metabolism-related proteins that may interact with matrine. Together, our study reveals matrine's capacity to upregulate LDLR expression and highlights its potential in treating HLP. These findings offer insights into matrine's mechanism of action and open new avenues for drug research and lipid metabolism regulation.

Exploring the Molecular Therapeutic Mechanisms of Gemcitabine through Quantitative Proteomics.

Gemcitabine (GEM) is widely employed in the treatment of various cancers, including pancreatic cancer. Despite their clinical success, challenges related to GEM resistance and toxicity persist. Therefore, a deeper understanding of its intracellular mechanisms and potential targets is urgently needed. In this study, through mass spectrometry analysis in data-dependent acquisition mode, we carried out quantitative proteomics (three independent replications) and thermal proteome profiling (TPP, two independent replications) on MIA PaCa-2 cells to explore the effects of GEM. Our proteomic analysis revealed that GEM led to the upregulation of the cell cycle and DNA replication proteins. Notably, we observed the upregulation of S-phase kinase-associated protein 2 (SKP2), a cell cycle and chemoresistance regulator. Combining SKP2 inhibition with GEM showed synergistic effects, suggesting SKP2 as a potential target for enhancing the GEM sensitivity. Through TPP, we pinpointed four potential GEM binding targets implicated in tumor development, including in breast and liver cancers, underscoring GEM's broad-spectrum antitumor capabilities. These findings provide valuable insights into GEM's molecular mechanisms and offer potential targets for improving treatment efficacy.

A novel conductive microtubule hydrogel for electrical stimulation of chronic wounds based on biological electrical wires.

Electrical stimulation (ES) is considered a promising therapy for chronic wounds via conductive dressing. However, the lack of a clinically suitable conductive dressing is a serious challenge. In this study, a suitable conductive biomaterial with favorable biocompatibility and conductivity was screened by means of an inherent structure derived from the body based on electrical conduction in vivo. Ions condensed around the surface of the microtubules (MTs) derived from the cell's cytoskeleton are allowed to flow in the presence of potential differences, effectively forming a network of biological electrical wires, which is essential to the bioelectrical communication of cells. We hypothesized that MT dressing could improve chronic wound healing via the conductivity of MTs applied by ES. We first developed an MT-MAA hydrogel by a double cross-linking method using UV and calcium chloride to improve chronic wound healing by ES. In vitro studies showed good conductivity, mechanical properties, biocompatibility, and biodegradability of the MT-MAA hydrogel, as well as an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to ES. The in vivo experimental results from a full-thickness diabetic wound model revealed rapid wound closure within 7d in C57BL/6J mice, and the wound bed dressed by the MT-MAA hydrogel was shown to have promoted re-epithelization, enhanced angiogenesis, accelerated nerve growth, limited inflammation phases, and improved antibacterial effect under the ES treatment. These preclinical findings suggest that the MT-MAA hydrogel may be an ideal conductive dressing for chronic wound healing. Furthermore, biomaterials based on MTs may be also promising for treating other diseases.

PROS1 is a crucial gene in the macrophage efferocytosis of diabetic foot ulcers: a concerted analytical approach through the prisms of computer analysis.

BACKGROUND: Diabetic foot ulcers (DFUs) pose a serious long-term threat because of elevated mortality and disability risks. Research on its biomarkers is still, however, very limited. In this paper, we have effectively identified biomarkers linked with macrophage excretion in diabetic foot ulcers through the application of bioinformatics and machine learning methodologies. These findings were subsequently validated using external datasets and animal experiments. Such discoveries are anticipated to offer novel insights and approaches for the early diagnosis and treatment of DFU. METHODS: In this work, we used the Gene Expression Omnibus (GEO) database's datasets GSE68183 and GSE80178 as the training dataset to build a gene model using machine learning methods. After that, we used the training and validation sets to validate the model (GSE134431). On the model genes, we performed enrichment analysis using both gene set variant analysis (GSVA) and gene set enrichment analysis (GSEA). Additionally, the model genes were subjected to immunological association and immune function analyses. RESULTS: In this study, PROS1 was identified as a potential key target associated with macrophage efflux in DFU by machine learning and bioinformatics approaches. Subsequently, the key biomarker status of PROS1 in DFU was also confirmed by external datasets. In addition, PROS1 also plays a key role in macrophage exudation in DFU. This gene may be associated with macrophage M1, CD4 memory T cells, naïve B cells, and macrophage M2, and affects IL-17, Rap1, hedgehog, and JAK-STAT signaling pathways. CONCLUSIONS: PROS1 was identified and validated as a biomarker for DFU. This finding has the potential to provide a target for macrophage clearance of DFU.

Effect of total astragalosides on diabetic non-healing wound by regulating immune microenvironment.

Aim: The aim of the research was to analyse the regulatory effect of astragaloside (AST) on the immune microenvironment of diabetic non-healing wound (DNHW), and to analyse the clinical efficacy and mechanism of wound repair in multiple layers. Material and methods: Ninety adult male Wistar rats, which were kept healthy (SPF) under natural infection, were randomly divided into three groups, namely, blank, control and observation groups, with 30 rats in each group. After adaptive feeding for 7 days, the diabetes model was established. After the model was formed, the wounds were uniformly prepared, and then the blank group only was shaved. Both the control group and the observation group were treated with moist exposure therapy. The control group was covered with physiological saline gauze, while the observation group was covered with AST gauze. The healing status of the wounds in both groups was observed and recorded on the 1st, 7th, and 14th days after formation. And the levels of α-smooth muscle actin (α-SMA) and collagen I (COL-1) in the wound tissue were measured. Results: On the 1st day after wound formation, the wound healing area, α-SMA, and COL-1 levels in the three groups were consistent (p > 0.05). On the 7th and 14th days after wound formation, the wound healing area in the three groups increased compared within the group, but only the control and observation groups had significantly higher wound healing area than on the 1st day after wound formation (p < 0.05). In addition, the blank group had lower levels of α-SMA and COL-1, while the control and observation groups had higher levels of α-SMA and COL-1 (p < 0.05). In the comparison between groups, the wound healing area, α-SMA, and COL-1 levels in the control and observation groups were higher than those in the blank group, while the wound healing area, α-SMA, and COL-1 levels in the observation group were higher than those in the control group (p < 0.05). Conclusions: AST can regulate the immune microenvironment of DNHW, improve α-SMA and COL-1, and accelerate the wound healing of DNHW.

Epidemiology and prognostic factors for new-onset deep venous thrombosis after unicompartmental knee arthroplasty: a retrospective study.

BACKGROUND: Patients who underwent knee joint arthroplasty were at risk of venous thromboembolic events (VTEs), however, less studies were conducted to demonstrate the epidemiology and risk factors of deep venous thrombosis (DVT) following unicompartmental knee arthroplasty (UKA). Objective of this study was to explore the incidence and prognostic factors of DVT after UKA. METHODS: Patients who underwent primary UKA from December 2018 to June 2022 were recruited in this study. Demographic characteristics, operation related variables and laboratory index were extracted and analyzed. Receiver operating characteristic analysis was performed to detect the optimum cut-off value for variables of interest. Univariate and multivariate logistic analysis were performed to identify risk factors of DVT. RESULTS: 351 UKAs with a mean age of 65.4 ± 7.1 years were reviewed. After 12.9 ± 11.2 months follow-up, 35 DVTs were confirmed which indicating an incidence of 9.9%. The results showed that occupation (agricultural laborer) (P = 0.008), disease duration > 8.5 years (P = 0.035), operation time > 169 min (P = 0.003), intraoperative blood loss > 102 ml (P < 0.001), BMI > 26.8 kg/m 2 (P = 0.001), preoperative D-dimer > 0.29 mg/L (P = 0.001), prothrombin time < 10.7 s (P = 0.033) and INR < 0.98 (P = 0.032) between DVT and Non-DVT group were significantly different. Multivariate logistic regression analysis showed intraoperative blood loss > 102 ml (OR, 3.707; P, 0.001), BMI > 26.8 kg/m 2 (OR, 4.664; P, 0.004) and D-dimer > 0.29 mg/L (OR, 2.882; P, 0.009) were independent risk factors of DVT after UKA. CONCLUSION: The incidence of DVT in the present study was 9.9%, extensive intraoperative blood loss, advanced BMI and high level of D-dimer would increase the risk of lower extremity thrombosis by 2-4 times.

Exploring the mechanism of contact-dependent cell-cell communication on chemosensitivity based on single-cell high-throughput drug screening platform.

High-throughput drug screening (HTDS) has significantly reduced the time and cost of new drug development. Nonetheless, contact-dependent cell-cell communication (CDCCC) may impact the chemosensitivity of tumour cells. There is a pressing need for low-cost single-cell HTDS platforms, alongside a deep comprehension of the mechanisms by which CDCCC affects drug efficacy, to fully unveil the efficacy of anticancer drugs. In this study, we develop a microfluidic chip for single-cell HTDS and evaluate the molecular mechanisms impacted by CDCCC using quantitative mass spectrometry-based proteomics. The chip achieves high-quality drug mixing and single-cell capture, with single-cell drug screening results on the chip showing consistency with those on the 96-well plates under varying concentration gradients. Through quantitative proteomic analysis, we deduce that the absence of CDCCC in single tumour cells can enhance their chemoresistance potential, but simultaneously subject them to stronger proliferation inhibition. Additionally, pathway enrichment analysis suggests that CDCCC could impact several signalling pathways in tumour single cells that regulate vital biological processes such as tumour proliferation, adhesion, and invasion. These results offer valuable insights into the potential connection between CDCCC and the chemosensitivity of tumour cells. This research paves the way for the development of single-cell HTDC platforms and holds the promise of advancing tumour personalized treatment strategies.

Urea fertilization increased CO2 and CH4 emissions by enhancing C-cycling genes in semi-arid grasslands.

Global climate change is predicted to increase exogenous N input into terrestrial ecosystems, leading to significant changes in soil C-cycling. However, it remains largely unknown how these changes affect soil C-cycling, especially in semi-arid grasslands, which are one of the most vulnerable ecosystems. Here, based on a 3-year field study involving N additions (0, 25, 50, and 100 kg ha-1 yr-1 of urea) in a semi-arid grassland on the Loess Plateau, we investigated the impact of urea fertilization on plant characteristics, soil properties, CO2 and CH4 emissions, and microbial C cycling genes. The compositions of genes involved in C cycling, including C fixation, degradation, methanogenesis, and methane oxidation, were determined using metagenomics analysis. We found that N enrichment increased both above- and belowground biomasses and soil organic C content, but this positive effect was weakened when excessive N was input (N100). N enrichment also altered the C-cycling processes by modifying C-cycle-related genes, specifically stimulating the Calvin cycle C-fixation process, which led to an increase in the relative abundance of cbbS, prkB, and cbbL genes. However, it had no significant effect on the Reductive citrate cycle and 3-hydroxypropionate bi-cycle. N enrichment led to higher soil CO2 and CH4 emissions compared to treatments without added N. This increase showed significant correlations with C degradation genes (bglA, per, and lpo), methanogenesis genes (mch, ftr, and mcr), methane oxidation genes (pmoA, pmoB, and pmoC), and the abundance of microbial taxa harboring these genes. Microbial C-cycling genes were primarily influenced by N-induced changes in soil properties. Specifically, reduced soil pH largely explained the alterations in methane metabolism, while elevated available N levels were mainly responsible for the shift in C fixation and C degradation genes. Our results suggest that soil N enrichment enhances microbial C-cycling processes and soil CO2 and CH4 emissions in semi-arid ecosystems, which contributes to more accurate predictions of ecosystem C-cycling under future climate change.

Full-length transcriptome characterization of Platycladus orientalis based on the PacBio platform.

As a unique and native conifer in China, Platycladus orientalis is widely used in soil erosion control, garden landscapes, timber, and traditional Chinese medicine. However, due to the lack of reference genome and transcriptome, it is limited to the further molecular mechanism research and gene function mining. To develop a full-length reference transcriptome, tissues from five different parts of P. orientalis and four cone developmental stages were sequenced and analyzed by single-molecule real-time (SMRT) sequencing through the PacBio platform in this study. Overall, 37,111 isoforms were detected by PacBio with an N50 length of 2,317 nt, an average length of 1,999 bp, and the GC content of 41.81%. Meanwhile, 36,120 coding sequences, 5,645 simple sequence repeats (SSRs), 1,201 non-coding RNAs (lncRNAs), and 182 alternative splicing (AS) events with five types were identified using the results obtained from the PacBio transcript isoforms. Furthermore, 1,659 transcription factors (TFs) were detected and belonged to 51 TF families. A total of 35,689 transcripts (96.17%) were annotated through the NCBI nr, KOG, Swiss-Prot and KEGG databases, and 385 transcript isoforms related to 8 types of hormones were identified incorporated into plant hormone signal transduction pathways. The assembly and revelation of the full-length transcriptome of P. orientalis offer a pioneering insight for future investigations into gene function and genetic breeding within Platycladus species.

Extracellular vesicles secreted by bone marrow stem cells mediate angiogenesis for the treatment of diabetic ulcers: A systematic review and meta-analysis of preclinical studies.

Background: Diabetic ulcers (DUs) typically occur in patients with vascular diseases and diabetes. Extracellular vesicles secreted by bone marrow-derived stem cells (BMSC-EVs) represent a cell-free therapy that has emerged as a promising alternative for treating DU, especially due to significant advancements in the understanding of their role in promoting angiogenesis; however, their application in DU treatment remains in the preclinical stage, and their effectiveness is still uncertain. Therefore, we conducted this meta-analysis to evaluate the therapeutic efficacy of BMSC-EVs in treating DU and to expedite the clinical translation of BMSC-EV therapy for DU. Methods: We conducted a comprehensive search of PubMed, Cochrane Library, MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and our self-constructed database of Chinese Biomedical Literature up to May 2023 to identify preclinical studies related to the therapeutic use of extracellular vesicles secreted by bone marrow-derived stem cells for treating diabetic ulcers. Outcome measures included wound healing rate, neovascularization density, a-sma, and CD31. RevMan 5 software was employed for all statistical analyses. Results: In this meta-analysis, a total of 11 studies involving 103 animals were identified. The pooled analysis indicated that BMSC-EV treatment showed a superior wound healing rate compared to that of the control group (SMD = 1.06, 95% CI [0.52, 1.60], P = 0.0001). In the subgroup analysis, EV combined with new materials or drug therapy performed better than the sole injection of extracellular vesicles (SMD = 1.85, 95% CI [0.87, 2.82], P < 0.00001). BMSC-EV treatment also resulted in a higher number of neovascular structures compared to the control group(SMD = 5.80, 95% CI[0.89,10.71], P = 0.006). In the subgroup analysis, EV combined therapy showed a significant difference in the number of blood vessels compared to the sole injection of extracellular vesicles (SMD = 4.90, 95% CI[2.64,7.15], P < 0.00001). However, BMSCs-EV treatment did not demonstrate any statistically significant difference in the angiogenesis-related indicators CD31 and α-SMA compared to the control group (SMD = 1.61, 95% CI[-0.51,3.74], P = 0.14). Conclusion: According to the current meta-analysis, BMSC-EV therapy can enhance the healing of diabetic ulcers and promote wound angiogenesis, particularly when used in combination with novel dressings or other drugs, which further accelerates the healing process of diabetic ulcers. To establish the most effective parameters for EV treatment in diabetic ulcers, future research should promptly progress into clinical trials.