Meningeal lymphatic vessel crosstalk with central nervous system immune cells in aging and neurodegenerative diseases.

Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.

A genome-wide CRISPR/Cas9 knockout screen identifies SEMA3F gene for resistance to cyclin-dependent kinase 4 and 6 inhibitors in breast cancer.

BACKGROUND: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer. METHODS: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models. RESULTS: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases. CONCLUSION: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

Magnetical scafford with ROS-scavenging for bone regeneration under static magnetic field.

Excessive reactive oxygen species (ROS) and bacterial infection significantly disrupt the microenvironment of tissue regeneration. Magnetic nanoparticles in combination with magnetic fields are emerging strategies to regulate tissue regeneration. In this work, ZnFe2O4 (ZFO) nanoparticles were prepared and subsequently decorated with polydopamine (PDA) and RGD peptide. The modified ZFO nanoparticles were loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as PP-ZFO/PDA-RGD magnetic scaffolds. Physicochemical, anti-ROS, antibacterial and osteogenic properties were evaluated in vitro. Under 30 mT static magnetic field, the PP-ZFO/PDA-RGD scaffold significantly enhanced the expression of ALP, RUNX2, BMP2 and mineralized nodules. It indicated that the magnetic system could promote the attachment, proliferation, differentiation and mineralization of MC3T3-E1 cells. The scaffold showed excellent ROS scavenging ability via the additive effect of ZFO, PDA and RGD. The remarkable antibacterial properties of Zn²âº and Fe³âº endowed the scaffolds with excellent antibacterial activity against E. coli and S. aureus. These results demonstrate that the PP-ZFO/PDA-RGD based magnetic system is a promising approach for bone regeneration under complex microenvironment.

Network pharmacology provides new insights into the mechanism of traditional Chinese medicine and natural products used to treat pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a rare cardiovascular disease with high morbidity and mortality rates. It is characterized by increased pulmonary arterial pressure. Current research into relevant therapeutic drugs and targets for PH, however, is insufficient still. Traditional Chinese medicine (TCM) and natural products have a long history as therapeutics for PH. Network pharmacology is an approach that integrates drug-target interactions and signaling pathways based on biomarkers information obtained from drug and disease databases. The concept of network pharmacology shows many similarities with the TCM philosophy. Network pharmacology help elucidate the mechanisms of TCM in PH. This review presents representative applications of network pharmacology in the study of the mechanisms of TCM and natural products for the treatment of PH. METHODS: In this review, we used ("pulmonary hypertension" OR "pulmonary arterial hypertension" OR "chronic thromboembolic pulmonary hypertension") AND ("network pharmacology" OR "systematic pharmacology") as keywords to search for reports from PubMed, Web of Science, and Google Scholar databases from ten years ago. The studies were screened and those chosen are summarized here. The TCM and natural products inPH and their corresponding targets and signaling pathways are described. Additionally, we discuss the application of network pharmacology in the study of TCM in PH to provide insights for future application strategies. RESULTS: Network pharmacology have shown that AKT-related pathways, HIF-1 signaling pathway, MAPK signaling pathway, TGF-ß-Smad pathway, cell cycle-related pathways and inflammation-related pathways are the main signaling pathways enriched in the PH targets of TCM. Reservatrol, curcumol, genistin, formononetin, wogonin, luteolin, baicalein, berberine, triptolide and tanshinone llA are active ingredients specific for PH treatment. A number of databases and tools specific for the treatment of PH are used in network pharmacology and natural product research. CONCLUSION: Through the reasonable combination of molecular docking, omics technology and bioinformatics technology, the mechanism of multi-targets can be explained more comprehensively. Analyzing the complex mechanism of TCM from the clinical perspective may be a potential development trend of network pharmacology. Combination of predicted targets and traditional pharmacology improves efficiency of drug development.

Development of barley proteins into peptides nanomicelles for encapsulation of hydrophobic bioactive ingredient.

BACKGROUND: As natural polymer materials, barley proteins have been utilized to fabricate nanocarriers to encapsulate and delivery hydrophobic bioactive ingredients. However, as a result of the high proportion of hydrophobic amino acids and structural rigidity, barley protein-based nanocarriers tend to aggregate easily and have a low loading capacity, which greatly limits their application. In the present study, barley proteins were enzymolyzed to fabricate nanomicelles and then applied to encapsulate hydrophobic bioactive ingredient. RESULTS: Self-assembled barley peptides could be obtained by controllable enzymolysis of barley proteins. The obtained barley peptides could self-assemble into nanomicelles (BPNMs) with a diameter of approximately 90 nm when the concentration was > 2.1 µg mL-1. Hydrophobic interaction, disulfide bonds and hydrogen bonds were involved in maintaining the structure of BPNMs. Six self-assembled peptides (QQPFPQ, QTPLPQ, QLPQIPE, QPFPQQPQLPH, QPFPQQPPFGL and QPFPQQPPFWQQQ) were identified and they were characterized by alternating arrangement of hydrophobic amino acids and hydrophilic amino acids. Moreover, BPNMs were utilized to encapsulate hydrophobic bioactive ingredient quercetin. When quercetin was encapsulated by BPNMs, its water solubility was significantly increased, being approximately 30-fold higher than free quercetin. Meanwhile, encapsulation of BPNMs could greatly increase quercetin stability. The interaction between BPNMs and quercetin occurred spontaneously, mainly driven by van der Waals forces and hydrogen bonds. CONCLUSION: In the present study, BPNMs were successfully developed and could be used as a promising delivery system to improve the water solubility and stability of hydrophobic bioactive ingredients. © 2024 Society of Chemical Industry.

Synergistic immunotherapy with a calcium-based nanoinducer: evoking pyroptosis and remodeling tumor-associated macrophages for enhanced antitumor immune response.

The challenges posed by low immunogenicity and the immunosuppressive tumor microenvironment (TME) significantly hinder the efficacy of cancer immunotherapy. Pyroptosis, characterized as a pro-inflammatory cell death pathway, emerges as a promising approach to augment immunotherapy by promoting immunogenic cell death (ICD). The predominance of M2 phenotype tumor-associated macrophages (TAMs) in the TME underscores the critical need for TAM reprogramming to mitigate this immunosuppression. Herein, we introduce a calcium-based, intelligent-responsive nanoinducer (CaZCH NPs), designed to concurrently initiate pyroptosis and remodel TAMs, thereby amplifying antitumor immunotherapy effects. Modified with hyaluronic acid, CaZCH NPs can target tumor cells. Once internalized, CaZCH NPs respond to the acidic environment, releasing Ca2+, curcumin and H2O2 to induce mitochondrial Ca2+ overload and oxidation stress, leading to caspase-3/GSDME-mediated cell pyroptosis. Concurrently, O2 produced by CaZCH and pro-inflammatory cytokines from pyroptotic cells work together to shift TAM polarization towards the M1 phenotype, effectively countering TME's immunosuppressive effect. Notably, the synergistic effect of Ca2+-mediated pyroptosis and TAM remodeling demonstrates superior antitumor efficiency in colorectal cancer models. The induced ICD, coupled with M1-type TAMs, effectively enhances immunogenicity and mitigates immunosuppression, promoting dendritic cell maturation and activating CD8+ T cell-dependent systemic antitumor immunity. Our study presents a promising synergistic strategy for achieving highly efficient immunotherapy using a simple calcium-based nanoinducer.

A Novel Targeted Microtubules Transformable Nanopeptide System Yields Strong Anti-Prostate Cancer Effects by Suppressing Nuclear Translocation of Androgen Receptors.

The extended use of androgen deprivation therapy (ADT) may often lead to the progression from castration-sensitive prostate cancer (CSPC) to castration-resistant prostate cancer (CRPC) in prostate cancer. To address this, it is essential to inhibit the nuclear translocation of the androgen receptor (AR) as part of an effective disease-modifying strategy. Microtubules play a central role in facilitating AR nuclear translocation, highlighting their importance as a therapeutic target. In this regard, a designated as the targeted microtubules transformable nanopeptide system (MTN) is developed. This system is designed to disrupt microtubule structure and function through dual-targeting of prostate-specific membrane antigen (PSMA) and ß-tubulin. Initially, MTN targets prostate cells via PSMA and then specifically binds to ß-tubulin within microtubules, leading to the formation of nanofibers. These nanofibers subsequently induce the polymerization of microtubules, thereby disrupting AR transport. Notably, MTN exhibits efficient and prolonged suppression of prostate cancer across the spectrum from CSPC to CRPC, with a highly favorable safety profile in normal cells. These findings highlight the potential of MTN as a novel and promising approach for comprehensive prostate cancer therapy throughout its entire progression.

Leaching of per- and polyfluoroalkyl substances (PFAS) from food contact materials with implications for waste disposal.

Leaching of per- and polyfluoroalkyl substances (PFAS) during the post-consumer disposal of food contact materials (FCMs) poses a potential environmental threat but has seldom been evaluated. This study characterized the leaching behavior of PFAS and unidentified precursors from six common FCMs and assessed the impact of environmental conditions on PFAS release during disposal. The total concentration of 21 PFAS ranged from 3.2 to 377 ng/g in FCMs, with PFAS leachability into water varying between 1.1-42.8 %. Increasing temperature promoted PFAS leaching, with leached nine primary PFAS (∑9PFAS) reaching 46.3, 70.4, and 102 ng/L at 35, 45, and 55 â„ƒ, respectively. Thermodynamic analysis (∆G>0, ∆H>0, and ∆S<0) indicated hydrophobic interactions control PFAS leaching. The presence of dissolved organic matter in synthetic leachate increased the leached ∑9PFAS from 47.1 to 103 ng/L but decreased PFBS, PFOS, and 6:2 FTS leaching. The total release of seven perfluorocarboxylic acids (∑7PFCAs) from takeaway food packaging waste was estimated to be 0.3-8.2 kg/y to landfill leachate and 0.6-15.4 kg/y to incineration plant leachate, contributing 0.2-4.8 % and 0.1-3.2 % of total ∑7PFCAs in each leachate type. While the study presents a refined methodology for estimating PFAS release during disposal, future research is needed on the indirect contribution from precursors.

The association of aromatic amino acids with coronary artery disease and major adverse cardiovascular events in a Chinese population.

This study aimed to evaluate the relationship between aromatic amino acids (AAAs), - phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp) - and coronary artery disease (CAD) in a prospective study involving 2970 participants undergoing coronary angiography at Beijing Hospital. Serum levels of Phe, Tyr and Trp were analysed. The cross-sectional data revealed that serum Tyr and Trp levels were significantly and inversely associated with CAD. During a median follow-up period of 44 months, 343 major adverse cardiovascular events (MACEs) and 138 all-cause deaths were recorded. MACE included myocardial infarction, stroke, revascularisation and all-cause mortality. Low serum Trp levels predicted an increased risk of MACE and death. High serum Phe levels were linked to an increased risk of MACE, while low Tyr levels were associated with a higher risk of death. Collectively, our findings underscore a close correlation between AAAs and CAD, as well as their potential predictive value for adverse cardiovascular outcomes.

Genomic Functional Analysis of Novel Radiation-Resistant Species of Knollia sp. nov. S7-12T from the North Slope of Mount Everest.

Radiation protection is an important field of study, as it relates to human health and environmental safety. Radiation-resistance mechanisms in extremophiles are a research hotspot, as this knowledge has great application value in bioremediation and development of anti-radiation drugs. Mount Everest, an extreme environment of high radiation exposure, harbors many bacterial strains resistant to radiation. However, owing to the difficulties in studying them because of the extreme terrain, many remain unexplored. In this study, a novel species (herein, S7-12T) was isolated from the moraine of Mount Everest, and its morphology and functional and genomic characteristics were analyzed. The strain S7-12T is white in color, smooth and rounded, non-spore-forming, and non-motile and can survive at a UV intensity of 1000 J/m2, showing that it is twice as resistant to radiation as Deinococcus radiodurans. Radiation-resistance genes, including IbpA and those from the rec and CspA gene families, were identified. The polyphasic taxonomic approach revealed that the strain S7-12T (=KCTC 59114T =GDMCC 1.3458T) is a new species of the genus Knoellia and is thus proposed to be named glaciei. The in-depth study of the genome of strain S7-12T will enable us to gain further insights into its potential use in radiation resistance. Understanding how microorganisms resist radiation damage could reveal potential biomarkers and therapeutic targets, leading to the discovery of potent anti-radiation compounds, thereby improving human resistance to the threat of radiation.

Bioelectricity drives transformation of nitrogen and perfluorooctanoic acid in constructed wetlands: Performances and mechanisms.

In this study, constructed wetland-microbial fuel cell (CW-MFC) filled with modified basalt fiber (MBF) via iron modification was utilized for treating perfluorooctanoic acid (PFOA) containing sewage. Results showed the significant promotion by bioelectricity on ammonium and total nitrogen by 7.80-8.14 %. Although such enhancement was suppressed by PFOA, higher removal was still observed with closed circuit, and PFOA removal also increased by 9.05 %. Bioelectricity contributed to enrichment of bacteria involved in nitrifying (Nitrospira and Ellin6067), denitrifying (like Thauera and Dechloromonas), iron redox (Geobacter), and sulfate-reducing (Desulfobacter), aligned with up-regulated of functional genes, including amoA, narG , napA, narK, narS, nrfA, sulp and sqr. Enrichment of autohydrogenotrophic and sulfide-oxidizing autotrophic denitrifiers, and nitrate dependent iron oxidation bacteria by bioelectricity all promoted denitrification. Moreover, bioelectricity boosted relative abundance of organic compounds degradation enzymes, such as dehydrogenase, decarboxylase, and dehalogenase, supporting the enhancement on PFOA removal. Generally, PFOA was converted to short-chain perfluorocarboxylic acids (PFCAs) via decarboxylation, hydroxylation, HF elimination, hydrolysis, F- elimination, C-C bond scission, and dehydration in CW-MFC. The final PFCAs-products determined was perfluorobutyric acid. This work estimated feasibility of treating PFOA containing sewage by CM-MFC, and offered new insights on enhancing mechanisms of nitrogen and PFOA conversion.

Ultrasound-based Radiomics Analysis for Assessing Risk Factors Associated With Early Recurrence Following Surgical Resection of Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to explore the value of ultrasound-based radiomics analysis for early recurrence after surgical resection of hepatocellular carcinoma (HCC). METHODS: This retrospective study included 127 patients who underwent primary surgical resection for HCC between October 2019 and November 2021. The patients were subsequently divided into training and validation sets (7:3 ratio). All patients received preoperative routine ultrasound and contrast-enhanced ultrasound examination, with postoperative pathological confirmation of HCC. Radiomics features were extracted from maximum section of a two-dimensional ultrasound image. The least absolute shrinkage and selection operation logistic regression algorithm with 10-fold cross-validation was used to establish ultrasonic radiomics features. Logistic regression modelling was used to build models based on clinical and ultrasonic features (model 1, clinical-ultrasonic model), radiomics signature (model 2, ultrasonic radiomics model), and the combination (model 3, clinical-ultrasonic-radiomics model). Then, a nomogram model was established to predict the risk of early recurrence, and the application value of nomogram through internal verification was evaluated. RESULTS: Model 3 showed optimal diagnostic performance in both training set (area under the curve [AUC], 0.907) and validation set (AUC, 0.925), followed by the model 1 in training set (AUC, 0.846) and validation set (AUC, 0.855), both above two models performed better than model 2 in training set (AUC, 0.751) and validation set (AUC, 0.702) (p < 0.05). In the training set and validation set of model 3, the sensitivity were 83.3%, 77.8%, the specificity ware 95.8%, 100.0% and the C-index were 0.791, 0.778. CONCLUSION: The preoperative clinical-ultrasonic-radiomics model is anticipated to be a reliable tool for predicting the early recurrence of surgical resection of HCC.

Reactive capture of CO2 via amino acid.

Reactive capture of carbon dioxide (CO2) offers an electrified pathway to produce renewable carbon monoxide (CO), which can then be upgraded into long-chain hydrocarbons and fuels. Previous reactive capture systems relied on hydroxide- or amine-based capture solutions. However, selectivity for CO remains low (<50%) for hydroxide-based systems and conventional amines are prone to oxygen (O2) degradation. Here, we develop a reactive capture strategy using potassium glycinate (K-GLY), an amino acid salt (AAS) capture solution applicable to O2-rich CO2-lean conditions. By employing a single-atom catalyst, engineering the capture solution, and elevating the operating temperature and pressure, we increase the availability of dissolved in-situ CO2 and achieve CO production with 64% Faradaic efficiency (FE) at 50 mA cm-2. We report a measured CO energy efficiency (EE) of 31% and an energy intensity of 40 GJ tCO-1, exceeding the best hydroxide- and amine-based reactive capture reports. The feasibility of the full reactive capture process is demonstrated with both simulated flue gas and direct air input.

Recent Progress in the Synthesis of 3D Complex Plasmonic Intragap Nanostructures and Their Applications in Surface-Enhanced Raman Scattering.

Plasmonic intragap nanostructures (PINs) have garnered intensive attention in Raman-related analysis due to their exceptional ability to enhance light-matter interactions. Although diverse synthetic strategies have been employed to create these nanostructures, the emphasis has largely been on PINs with simple configurations, which often fall short in achieving effective near-field focusing. Three-dimensional (3D) complex PINs, distinguished by their intricate networks of internal gaps and voids, are emerging as superior structures for effective light trapping. These structures facilitate the generation of hot spots and hot zones that are essential for enhanced near-field focusing. Nevertheless, the synthesis techniques for these complex structures and their specific impacts on near-field focusing are not well-documented. This review discusses the recent advancements in the synthesis of 3D complex PINs and their applications in surface-enhanced Raman scattering (SERS). We begin by describing the foundational methods for fabricating simple PINs, followed by a discussion on the rational design strategies aimed at developing 3D complex PINs with superior near-field focusing capabilities. We also evaluate the SERS performance of various 3D complex PINs, emphasizing their advanced sensing capabilities. Lastly, we explore the future perspective of 3D complex PINs in SERS applications.

Antibacterial periodontal ligament stem cells enhance periodontal regeneration and regulate the oral microbiome.

BACKGROUND: The transplantation of periodontal ligament stem cells (PDLSCs) has been shown to enhance periodontal regeneration in animal models and clinical trials. However, it is not known whether PDLSCs are antibacterial and whether this affects oral microbiota and periodontal regeneration. METHODS: We isolated human PDLSCs from periodontal ligament of extracted teeth. Rats' periodontal fenestration defects were prepared, and treated with PDLSC injections (Cell group), using saline injections (Saline group) as the control. The oral microbiota was explored by 16 S rDNA sequencing and compared with that before surgery (PRE group). The antibacterial property of PDLSCs and its underlying mechanism were tested in vitro. RESULTS: Microbiome analyses reveal a decreased biodiversity, a changed community structure, and downregulated community functions of the oral microbiome in the Saline group. PDLSCs injections enhance periodontal regeneration, reverse the decrease in diversity, and increase the abundance of non-pathogenic bacterial Bifidobacterium sp. and Lactobacillus sp., making the oral microbiome similar to that of the PRE group. In vitro, PDLSCs inhibit the growth of Staphylococcus aureus, Escherichia coli, and Fusobacterium nucleatum. The main mechanism of action is postulated to involve production of the cationic antimicrobial peptide LL-37. CONCLUSIONS: Our findings reveal that PDLSC injections enhance periodontal regeneration and regulate the oral microbiome to foster an oral cavity microenvironment conducive to symbiotic microbiota associated with health.

[Comparative study of total knee arthroplasty assisted by robot and remote sensing navigation system].

OBJECTIVE: To compare clinical efficacy of robot-assisted (RA) and remote sensing navigation alignment (RSNA) system-assisted total knee arthroplasty (TKA). METHODS: From March 2023 to June 2023, 60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis (KOA) were admitted and divided into RSNA group and RA group according to different treatment methods, with 30 patients in each group. There were 5 males and 25 females in RSNA group, aged from 56 to 81 years old with an average of(66.33±7.16) years old;body mass index(BMI) ranged from 19.87 to 38.54 kg·m-2 with an average of (28.40±6.18) kg·m-2;the courses of disease ranged from 5 to 36 months with an average of (18.20±8.98) months; RSNA system was used to assist the positioning of osteotomy. There were 7 males and 23 females in RA group, aged from 55 to 82 years old with an average of (67.83±8.61) years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an average of (28.01±4.89) kg·m-2; the courses of disease ranged from 3 to 33 months with an average of (17.93±9.20) months;RA was performed. Operation time, incision length, latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups. Hip-knee ankle angle (HKAA), HKAA deviation, lateral distal femoral angle ( LDFA), medial proximal tibial angle (MPTA) and posterior tibial slope (PTS) were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society score (KSS) were used to evaluate functional recovery before operation, 3 and 6 months after operation. RESULTS: The operation was performed successfully in both groups, and there were no serious complications such as vascular and nerve injury during operation. The wound healed well at stageⅠafter operation, and the follow-up time was 6 months. The operation time, latent blood loss at 2 weeks after operation and incision length in RSNA group were (94.35±5.75) min, (130.54±17.53) ml and (14.73±2.14) cm, respectively;while (102.57±6.88) min, (146.33±19.47) ml and (16.78±2.32) cm in RA group, respectively. RSNA group was better than RA group (P<0.05). No deep vein thrombosis occurred in both groups at 2 weeks after operation, 5 patients occurred intermuscular vein thrombosisin in RSNA group and 8 patients in RA group, the difference was not statistically significant (P>0.05). In RSNA group, HKAA, LDFA and MPTA were (173.00±5.54) °, (86.96±3.45) °, (82.79±3.35) ° before operation, and (178.34±1.85) °, (89.92±0.42) °, (89.84±0.73) ° at 1 week after operation, respectively. In RA group, HKAA, LDFA and MPTA were (173.31±6.48) °, (87.15±3.40) ° and (82.99±3.05) ° before operation, and (178.52±1.79) °, (90.03±0.39) ° and (90.15±0.47) ° at 1 week after operation, respectively. HKAA, LDFA and MPTA were significantly improved in both groups at 1 week after operation (P<0.05). There were no significant difference in HKAA, LDFA, MPTA and PTS between two groups before operation and 1 week after operation (P>0.05). There was no significant difference in deviation distribution of HKAA at 1 week after operation (χ2=2.611, P=0.456). There were no significant difference in WOMAC and KSS between two groups before operation, 3 and 6 months after operation (P>0.05), and postoperative WOMAC and KSS at 3 and 6 months between two groups were improved compared with those before operation (P<0.05). CONCLUSION: Both RA and RSNA system assisted TKA could obtain accurate osteotomy, RA has higher surgical accuracy, RSNA system assisted operation has less trauma, and operation is simpler.

[Application of remote sensing navigation system in total knee arthroplasty].

OBJECTIVE: To explore clinical accuracy of remote sensing navigation alignment (RSNA) system in total knee arthroplasty (TKA) and its influence on postoperative clinical efficacy. METHODS: From May 2021 to May 2022, 60 knee osteoarthritis (KOA) patients with Kellgren-Lawrence (K-L) grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods, and 30 patients in each group. There were 6 males and 24 females in RSNA group, aged from 55 to 86 years old with an average of (68.06±8.23) years old;body mass index (BMI) ranged from 22.15 to 34.58 kg·m-2 with an average of (28.20±3.01) kg·m-2;the courses of disease ranged from 2 to 60 months with an average of (18.80±14.80) months;13 patients with grade Ⅲ and 17 patients with grade Ⅳ according to K-L grading. In traditional operation group, there were 8 males and 22 females, aged from 57 to 85 years old with an average of (67.26±6.32) years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of (27.49±2.32) kg·m-2;the courses of disease ranged from 3 to 60 months with an average of (21.30±16.44) months;14 patients with grade Ⅲ and 16 patients with grade Ⅳ according to K-L grading. Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Knee Society score(KSS) were used to evaluate functional recovery of patients. Hip-knee-ankle angle (HKAA), distal femoral valgus angle (FVA) and distal fermoral flexion angle (DFFA) were measured before operation. HKAA and HKAA deviation angle were measured at 1 week after operation, and defective rate of lower limb force line, femur prosthesis valgus angle (FPVA) and femoral prosthesis flexion angle (FPFA), respectively, were calculated. RESULTS: There were no serious complications such as vascular and nerve injury during operation, and wound healed at stage Ⅰ. Both groups were followed up for 6 months. There were no significant difference in WOMAC index, KSS, HKAA, FVA and DFFA between two groups before operation (P>0.05). The force line defect rate, HKAA, HKAA deviation angle, FPVA deviation angle and FPFA of RSNA group were 6.7%, (178.74±1.56) °, (1.25±1.56) °, (1.84±0.16) ° and (4.85±2.46) °, respectively;while in traditional operation group were 20%, (176.73±3.46) °, (3.27±3.46) °, (2.44±0.26) °, (6.60±1.86) °;the difference between two groups were statistically significant (P<0.05). There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation (P>0.05). CONCLUSION: RSNA system could reduce defective rate of lower limb force line, FPVA deviation angle and FPFA after TKA, which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Targeting ALDOA to modulate tumorigenesis and energy metabolism in retinoblastoma.

This study aims to elucidate the pivotal role of aldolase A (ALDOA) in retinoblastoma (RB) and evaluate the potential of the ALDOA inhibitor itaconate in impeding RB progression. Utilizing single-cell RNA sequencing, ALDOA consistently exhibits overexpression across diverse cell types, particularly in cone precursor cells, retinoma-like cells, and retinoblastoma-like cells. This heightened expression is validated in RB tissues and cell lines. ALDOA knockdown significantly diminishes RB cell viability, impedes colony formation, and induces notable metabolic alterations. RNA-seq analysis identifies SUSD2, ARHGAP27, and CLK2 as downstream genes associated with ALDOA. The application of itaconate demonstrates efficacy in inhibiting RB cell proliferation, validated through in vitro and in vivo models. This study emphasizes ALDOA as a promising target for innovative RB therapies, with potential implications for altering tumor energy metabolism.

Multiomics reveals microbial metabolites as key actors in intestinal fibrosis in Crohn's disease.

Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials.