Ecological insights into hematopoiesis regulation: unraveling the influence of gut microbiota.

The gut microbiota constitutes a vast ecological system within the human body, forming a mutually interdependent entity with the host. In recent years, advancements in molecular biology technologies have provided a clearer understanding of the role of the gut microbiota. They not only influence the local immune status and metabolic functions of the host's intestinal tract but also impact the functional transformation of hematopoietic stem cells (HSCs) through the gut-blood axis. In this review, we will discuss the role of the gut microbiota in influencing hematopoiesis. We analyze the interactions between HSCs and other cellular components, with a particular emphasis on the direct functional regulation of HSCs by the gut microbiota and their indirect influence through cellular components in the bone marrow microenvironment. Additionally, we propose potential control targets for signaling pathways triggered by the gut microbiota to regulate hematopoietic function, filling crucial knowledge gaps in the development of this research field.

Effective Activation of Peroxymonosulfate by Oxygen Vacancy Induced Musa Basjoo Biochar to Degrade Sulfamethoxazole: Efficiency and Mechanism.

Biochar materials have garnered attention as potential catalysts for peroxymonosulfate (PMS) activation due to their cost-effectiveness, notable specific surface area, and advantageous structural properties. In this study, a suite of plantain-derived biochar (MBB-400, MBB-600, and MBB-800), possessing a well-defined pore structure and a substantial number of uniformly distributed active sites (oxygen vacancy, OVs), was synthesized through a facile calcination process at varying temperatures (400, 600, and 800 °C). These materials were designed for the activation of PMS in the degradation of sulfamethoxazole (SMX). Experimental investigations revealed that OVs not only functioned as enriched sites for pollutants, enhancing the opportunities for free radicals (•OH/SO4•-) and surface-bound radicals (SBRs) to attack pollutants, but also served as channels for intramolecular charge transfer leaps. This role contributed to a reduction in interfacial charge transfer resistance, expediting electron transfer rates with PMS, thereby accelerating the decomposition of pollutants. Capitalizing on these merits, the MBB-800/PMS system displayed a 61-fold enhancement in the conversion rate for SMX degradation compared to inactivated MBB/PMS system. Furthermore, the MBB-800 exhibited less cytotoxicity towards rat pheochromocytoma (PC12) cells. Hence, the straightforward calcination synthesis of MBB-800 emerges as a promising biochar catalyst with vast potential for sustainable and efficient wastewater treatment and environmental remediation.

Enhanced articular cartilage regeneration using costal chondrocyte-derived scaffold-free tissue engineered constructs with ascorbic acid treatment.

Background: Cartilage tissue engineering faces challenges related to the use of scaffolds and limited seed cells. This study aims to propose a cost-effective and straightforward approach using costal chondrocytes (CCs) as an alternative cell source to overcome these challenges, eliminating the need for special culture equipment or scaffolds. Methods: CCs were cultured at a high cell density with and without ascorbic acid treatment, serving as the experimental and control groups, respectively. Viability and tissue-engineered constructs (TEC) formation were evaluated until day 14. Slices of TEC samples were used for histological staining to evaluate the secretion of glycosaminoglycans and different types of collagen proteins within the extracellular matrix. mRNA sequencing and qPCR were performed to examine gene expression related to cartilage matrix secretion in the chondrocytes. In vivo experiments were conducted by implanting TECs from different groups into the defect site, followed by sample collection after 12 weeks for histological staining and scoring to evaluate the extent of cartilage regeneration. Hematoxylin-eosin (HE), Safranin-O-Fast Green, and Masson's trichrome stainings were used to examine the content of cartilage-related matrix components in the in vivo repair tissue. Immunohistochemical staining for type I and type II collagen, as well as aggrecan, was performed to assess the presence and distribution of these specific markers. Additionally, immunohistochemical staining for type X collagen was used to observe any hypertrophic changes in the repaired tissue. Results: Viability of the chondrocytes remained high throughout the culture period, and the TECs displayed an enriched extracellular matrix suitable for surgical procedures. In vitro study revealed glycosaminoglycan and type II collagen production in both groups of TEC, while the TEC matrix treated with ascorbic acid displayed greater abundance. The results of mRNA sequencing and qPCR showed that genes related to cartilage matrix secretion such as Sox9, Col2, and Acan were upregulated by ascorbic acid in costal chondrocytes. Although the addition of Asc-2P led to an increase in COL10 expression according to qPCR and RNA-seq results, the immunofluorescence staining results of the two groups of TECs exhibited similar distribution and fluorescence intensity. In vivo experiments showed that both groups of TEC could adhere to the defect sites and kept hyaline cartilage morphology until 12 weeks. TEC treated with ascorbic acid showed superior cartilage regeneration as evidenced by significantly higher ICRS and O'Driscoll scores and stronger Safranin-O and collagen staining mimicking native cartilage when compared to other groups. In addition, the immunohistochemical staining results of Collgan X indicated that, after 12 weeks, the ascorbic acid-treated TEC did not exhibit further hypertrophy upon transplantation into the defect site, but maintained an expression profile similar to untreated TECs, while slightly higher than the sham-operated group. Conclusion: These results suggest that CC-derived scaffold-free TEC presents a promising method for articular cartilage regeneration. Ascorbic acid treatment enhances outcomes by promoting cartilage matrix production. This study provides valuable insights and potential advancements in the field of cartilage tissue engineering. The translational potential of this article: Cartilage tissue engineering is an area of research with immense clinical potential. The approach presented in this article offers a cost-effective and straightforward solution, which can minimize the complexity of cell culture and scaffold fabrication. This simplification could offer several translational advantages, such as ease of use, rapid scalability, lower costs, and the potential for patient-specific clinical translation. The use of costal chondrocytes, which are easily obtainable, and the scaffold-free approach, which does not require specialized equipment or membranes, could be particularly advantageous in clinical settings, allowing for in situ regeneration of cartilage.

Enhanced osteochondral regeneration with a 3D-Printed biomimetic scaffold featuring a calcified interfacial layer.

The integrative regeneration of both articular cartilage and subchondral bone remains an unmet clinical need due to the difficulties of mimicking spatial complexity in native osteochondral tissues for artificial implants. Layer-by-layer fabrication strategies, such as 3D printing, have emerged as a promising technology replicating the stratified zonal architecture and varying microstructures and mechanical properties. However, the dynamic and circulating physiological environments, such as mass transportation or cell migration, usually distort the pre-confined biological properties in the layered implants, leading to undistinguished spatial variations and subsequently inefficient regenerations. This study introduced a biomimetic calcified interfacial layer into the scaffold as a compact barrier between a cartilage layer and a subchondral bone layer to facilitate osteogenic-chondrogenic repair. The calcified interfacial layer consisting of compact polycaprolactone (PCL), nano-hydroxyapatite, and tasquinimod (TA) can physically and biologically separate the cartilage layer (TA-mixed, chondrocytes-load gelatin methacrylate) from the subchondral bond layer (porous PCL). This introduction preserved the as-designed independent biological environment in each layer for both cartilage and bone regeneration, successfully inhibiting vascular invasion into the cartilage layer and preventing hyaluronic cartilage calcification owing to devascularization of TA. The improved integrative regeneration of cartilage and subchondral bone was validated through gross examination, micro-computed tomography (micro-CT), and histological and immunohistochemical analyses based on an in vivo rat model. Moreover, gene and protein expression studies identified a key role of Caveolin (CAV-1) in promoting angiogenesis through the Wnt/ß-catenin pathway and indicated that TA in the calcified layer blocked angiogenesis by inhibiting CAV-1.

Influence of Subchondral Cysts on the Outcomes of Surgical Treatment for Osteochondral Lesions of the Talus: A Systematic Review and Meta-analysis.

Background: Limited literature is available regarding the effect of subchondral cysts on the surgical outcomes for treatment of osteochondral lesion of the talus (OLT). Purpose: To conduct a systematic review and meta-analysis of studies comparing surgical outcomes between OLTs with and without cysts. Study Design: Systematic review; Level of evidence, 4. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies published up to January 7, 2023. The 4375 retrieved studies were screened, and 9 articles (level of evidence, 2-4) were included, which comprised 165 patients with OLT and subchondral cysts (cyst group) and 223 without cysts (noncyst group). After data extraction, mean differences in outcome scores (American Orthopaedic Foot and Ankle Society [AOFAS] Ankle Hindfoot Scale, visual analog scale [VAS] score for pain) and adverse events were compared between the groups. Results: Functional scores improved after surgery in both groups, with the cyst group having a significantly higher AOFAS score than the noncyst group (P = .005; I2 = 0%); subgroup analysis revealed that this difference was attributable to the size of the osteochondral lesion and the type of surgical procedure. No significant difference was found between the cyst and noncyst groups in VAS pain scores (P = .77; I2 = 0%) or postoperative adverse events (P = .35; I2 = 0%). Conclusion: The results of this review indicated that patients with subchondral cysts improved with surgical treatment of OLT. A relatively low level of evidence was available to indicate that surgical treatment for small OLTs with subchondral cysts will result in better clinical outcomes compared with OLTs without cysts.

Comparative Analysis of Hyaline Cartilage Characteristics and Chondrocyte Potential for Articular Cartilage Repair.

This study aimed to compare the histological, biochemical, and mechanical characteristics of hyaline cartilage in different regions and evaluate the potential of chondrocytes extracted from each region as donor sources for articular cartilage repair. The cartilage tissues of the femoral head and knee joint, ribs, nasal septum, thyroid, and xiphoid process of adult Bama pigs were isolated for histological, biochemical, and mechanical evaluation and analysis. The corresponding chondrocytes were isolated and evaluated for proliferation and redifferentiation capacity, using biochemical and histological analysis and RT-PCR experiments. Compared with articular cartilage, non-articular hyaline cartilage matrix stained more intensely in Safranin-O staining. Glycosaminoglycan and total collagen content were similar among all groups, while the highest content was measured in nasal septal cartilage. Regarding biomechanics, non-articular cartilage is similar to articular cartilage, but the elastic modulus and hardness are significantly higher in the middle region of costal cartilage. The chondrocytes extracted from different regions had no significant difference in morphology. Hyaline cartilage-like pellets were formed in each group after redifferentiation. The RT-PCR results revealed similar expressions of cartilage-related genes across the groups, albeit with lower expression of Col2 in the xiphoid chondrocytes. Conversely, higher expression of Col10 was observed in the chondrocytes from the rib, thyroid, and xiphoid cartilage. This study provides valuable preclinical data for evaluating heterotopic hyaline cartilage and chondrocytes for articular cartilage regeneration. The findings contribute to the selection of chondrocyte origins and advance the clinical translation of technology for cartilage regeneration.

Boosting the Performances of Semitransparent Organic Photovoltaics via Synergetic Near-Infrared Light Management.

Semitransparent organic photovoltaics (ST-OPVs) offer promising prospects for application in building-integrated photovoltaic systems and greenhouses, but further improvement of their performance faces a delicate trade-off between the two competing indexes of power conversion efficiency (PCE) and average visible transmittance (AVT). Herein, the authors take advantage of coupling plasmonics with the optical design of ST-OPVs to enhance near-infrared absorption and hence simultaneously improve efficiency and visible transparency to the maximum extent. By integrating core-bishell PdCu@Au@SiO2 nanotripods that act as optically isotropic Lambertian sources with near-infrared-customized localized surface plasmon resonance in an optimal ternary PM6:BTP-eC9:L8-BO-based ST-OPV, it is shown that their interplay with a multilayer optical coupling layer, consisting of ZnS(130 nm)/Na3AlF6(60 nm)/WO3(100 nm)/LaF3(50 nm) identified from high-throughput optical screening, leads to a record-high PCE of 16.14% (certified as 15.90%) along with an excellent AVT of 33.02%. The strong enhancement of the light utilization efficiency by ≈50% as compared to the counterpart device without optical engineering provides an encouraging and universal pathway for promoting breakthroughs in ST-OPVs from meticulous optical design.

Electrophysiological and Behavioral Responses of Batocera horsfieldi Hope to Volatiles from Pistacia chinensis Bunge.

Following infestation by phytophagous insects, changes in the composition and relative proportion of volatile components emitted by plants may be observed. Some phytophagous insects can accurately identify these compounds to locate suitable host plants. We investigated whether herbivore-induced plant volatiles (HIPVs) generated by herbivory on Pistacia chinensis Bunge (Sapindales: Aceraceae) might be semiochemicals for the host location of Batocera horsfieldi Hope (Coleoptera: Cerambycidae). We performed two-choice bioassays (indoor darkroom, inside cages) on plants damaged by adult feeding and intact control plants. Volatiles from these plants were then collected and identified, and the response of adult antennae to these compounds was tested via electroantennography (EAG). The behavioral responses of B. horsfieldi to these compounds were finally assessed using a Y-tube olfactometer. Host plant choice tests show that B. horsfieldi prefers feeding-damaged P. chinensis over healthy trees. In total, 15 compounds were collected from healthy and feeding-damaged P. chinensis, 10 of which were shared in both healthy and feeding-damaged P. chinensis, among which there were significant differences in the quantities of five terpenes, including α-pinene, ß-pinene, α-phellandrene, D-limonene, and ß-ocimene. In EAG assays, the antennae of B. horsfieldi adults responded strongly to (Z)-3-hexen-1-ol, ß-ocimene, 3-carene, γ-terpinene, D-limonene, myrcene, and α-phellandrene. The antennae of B. horsfieldi adults responded in a dose-response manner to these compounds. Y-tube behavioral experiments showed that four compounds attracted mated females ((Z)-3-hexen-1-ol, ß-ocimene, 3-carene, and α-phellandrene), two compounds ((Z)-3-hexen-1-ol and α-phellandrene) attracted males, and adults of both sexes avoided D-limonene. Feeding bioassays showed that (Z)-3-hexen-1-ol and ß-ocimene could promote the feeding of B. horsfieldi and that D-limonene inhibited this response. These results could provide a theoretical basis for developing attractants or repellents for B. horsfieldi.

VEGF/Nrp1/HIF-1α promotes proliferation of hepatocellular carcinoma through a positive feedback loop.

To investigate the role of neuropilin1 (Nrp1) in glucose metabolism and proliferation of hepatocellular carcinoma (HCC) cells and to analyze its mechanism of action. The CRISPR gene knockout technique was used to knock out the Nrp1 gene in two HCC cell lines. The effect of Nrp1 on the proliferation of HCC cells was assessed in the CCK8 assay and plate cloning assay. The expression levels of glucose consumption, lactate production, and essential proteins of the glycolytic pathway were detected to explore the effect of Nrp1 on glucose metabolism in HCC cells. Using CoCl2 to revert the expression of hypoxia inducible factor-1α (HIF-1α), the role of HIF-1α in the pro-HCC cell metabolism of Nrp1 were demonstrated. The protein synthesis inhibitor CHX and proteasome inhibitor MG-132 was used to analyze the molecular mechanism of action of Nrp1 on HIF-1α. The Kaplan-Meier method was used to calculate survival rates and plot survival curves. Based on the CCK8 assay and plate cloning assay, we found that Nrp1 knockout significantly inhibited the proliferation of HCC cells. Nrp1 inhibitor suppressed lactate production and glucose consumption in HCC cells. Knockout of Nrp1 decreased the expression of glycolytic pathway-related proteins and HIF-1α protein. Furthermore, by joint use of CoCl2 and NRP1 knockout, we confirmed that reverting HIF-1α expression could reverse the effect of Nrp1 knockout on HCC cell metabolism in vitro. Mechanistically, Nrp1 showed a close correlation with the stability of HIF-1α protein in protein stability assay. Finally, we revealed that high expression of Nrp1 in HCC tissues was associated with poor overall survival and disease-free survival of the patients. Nrp1 accelerates glycolysis and promotes proliferation of HCC by regulating HIF-1α protein stability and through the VEGF/Nrp1/HIF-1α positive feedback loop.

Costal Cartilage Graft Repair Osteochondral Defect in a Mouse Model.

OBJECTIVE: Osteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation. DESIGN: Costal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes. RESULTS: At 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur. CONCLUSION: Costal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.

Effect of surgical approach on the treatment of Morton's neuroma: a systematic review and meta-analysis.

BACKGROUND: Surgical resection of Morton's neuroma includes dorsal and plantar approaches. However, there is no consensus on the choice of approach in clinic. The purpose of this study was to conduct a systematic review and meta-analysis to compare the surgical results of dorsal and plantar approaches. METHODS: The literatures of PubMed, Cochrane library, Embase and Web of Science were searched on April 26th, 2023. A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The data were extracted after screening the literature and evaluating the quality of the methodology included in the study. The RevMan5.4 software was used to analyze and calculate the OR value and 95% confidence interval. RESULTS: A total of 7 randomized controlled trials and comparative studies were published, of which only 5 were included. There were 158 feet via plantar approach (plantar group, PG) and 189 via dorsal approach (dorsal group, DG). There was no significant difference between PG and DG in overall adverse events, sensory problems, incision infection and deep vein thrombosis (p > 0.05). In terms of scar problems, PG showed more than DG (OR, 2.90[95%CI, 1.40 to 5.98]; p = 0.004). Other outcome indicators such as visual analogue scale (VAS) scores and American Orthopedic Foot and Ankle Society (AOFAS) scores were difficult to be included in the comparison. CONCLUSIONS: Based on the relatively low quality and small amount of available evidence, the meta-analysis conducted produces a hypothesis that the frequency of adverse events in surgical treatment of Morton's neuroma, dorsal approach and plantar approach may be the same, but the types are different. More high-level evidence is needed to further verify this hypothesis.

Revealing a 3D Fermi Surface Pocket and Electron-Hole Tunneling in UTe_{2} with Quantum Oscillations.

Spin triplet superconductor UTe_{2} is widely believed to host a quasi-two-dimensional Fermi surface, revealed by first-principles calculations, photoemission, and quantum oscillation measurements. An outstanding question still remains as to the existence of a three-dimensional Fermi surface pocket, which is crucial for our understanding of the exotic superconducting and topological properties of UTe_{2}. This 3D Fermi surface pocket appears in various theoretical models with different physics origins, but has not been unambiguously detected in experiment. Here for the first time we provide concrete evidence for a relatively isotropic, small Fermi surface pocket of UTe_{2} via quantum oscillation measurements. In addition, we observed high frequency quantum oscillations corresponding to electron-hole tunneling between adjacent electron and hole pockets. The coexistence of 2D and 3D Fermi surface pockets, as well as the breakdown orbits, provide a test bed for theoretical models and aid the realization of a unified understanding of the superconducting state of UTe_{2} from the first-principles approach.

Shinella sedimenti sp. nov., isolated from sediment of Zhairuo Island located in the East China Sea.

A Gram-negative, rod-shaped and aerobic bacterial strain B3.7T, was isolated from the sediment of Zhairuo Island, Zhoushan city, Zhejiang Province, PR China. Maximum growth of strain B3.7T was observed at 30 °C when cultured in a medium containing 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strain B3.7T belonged to the genus Shinella; it showed the highest sequence similarity of 98.47 % to Shinella kummerowiae CCBAU 25048T. The average nucleotide identity and digital DNA-DNA hybridization values between strain B3.7T and its reference strains were 82.9-84.2 % and 26.1-27.3 %, respectively. Chemotaxonomic analysis indicated that the sole respiratory quinone was Q-10 and the predominant cellular fatty acids were C19 : 0 cyclo ω8c, C16 : 0, C18 : 1 ω7c 11-methyl and summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified phospholipids and two unidentified aminolipids. Collectively, strain B3.7T can be considered to represent a novel species, for which the name Shinella sedimenti sp. nov. is proposed. The type strain is B3.7T (=MCCC 1K07163T=LMG 32559T).

A Simulation of Thermal Management Using a Diamond Substrate with Nanostructures.

In recent years, the rapid progress in the field of GaN-based power devices has led to a smaller chip size and increased power usage. However, this has given rise to increasing heat aggregation, which affects the reliability and stability of these devices. To address this issue, diamond substrates with nanostructures were designed and investigated in this paper. The simulation results confirmed the enhanced performance of the device with diamond nanostructures, and the fabrication of a diamond substrate with nanostructures is demonstrated herein. The diamond substrate with square nanopillars 2000 nm in height exhibited optimal heat dissipation performance. Nanostructures can effectively decrease heat accumulation, resulting in a reduction in temperature from 121 °C to 114 °C. Overall, the simulation and experimental results in this work may provide guidelines and help in the development of the advanced thermal management of GaN devices using diamond micro/nanostructured substrates.

The efficacy of fat-free mass index and appendicular skeletal muscle mass index in cancer malnutrition: a propensity score match analysis.

Background: Reduced muscle mass (RMM) is a phenotypic criterion for malnutrition; the appendicular skeletal muscle mass index (ASMI) and fat-free mass index (FFMI) are both applicable indicators in the global leadership initiative on malnutrition (GLIM) guideline. However, their sensitivity and prognostic effect remain unclear. Methods: Clinical data of 2,477 patients with malignant tumors were collected. Multi-frequency bioelectrical impedance analysis was used to obtain ASMI and FFMI. RMM was confirmed by ASMI (< 7.0 kg/m2 for men and < 5.7 kg/m2 for women) or FFMI (< 17 kg/m2 for men and < 15 kg/m2 for women). Propensity score match analysis and logistic regression analysis were used to evaluate the efficacy of FFMI and ASMI in diagnosing severe malnutrition and multivariate Cox regression analysis to determine the efficacy of RMM in predicting survival. Results: In total, 546 (22.0%) and 659 (26.6%) participants were diagnosed with RMM by ASMI (RMM.ASMI group) and FFMI (RMM.FFMI group); 375 cases overlapped. Body mass index (BMI), midarm circumference, triceps skinfold thickness, and maximum calf circumference were all significantly larger in the RMM.FFMI group for both sexes (P < 0.05). A 1:1 matched dataset constructed by propensity score match contained 810 cases. RMM.FFMI was an influential factor of severe malnutrition with HR = 3.033 (95% CI 2.068-4.449, P < 0.001), and RMM.ASMI was a predictive factor of overall survival (HR = 1.318, 95% CI 1.060-1.639, P = 0.013 in the RMM.ASMI subgroup, HR = 1.315, 95% CI 1.077-1.607, P = 0.007 in the RMM.FFMI subgroup). Conclusion: In general, RMM indicates negative clinical outcomes; when defined by FFMI, it predicts nutritional status, and when defined by ASMI, it is related to poor survival in cancer patients.

Association of Neutrophil-to-Lymphocyte Ratio with Nutrition in Patients with Various Types of Malignant Tumors: A Multicenter Cross-Sectional Study.

Aim: Neutrophil-to-lymphocyte ratio (NLR) is an index of systemic inflammation. This study is to clarify the role of NLR in body functional status, nutritional risk and nutritional status in the course of tumor. Methods: A multi-center cross-sectional study of patients with various types of malignant tumors was accrued from the whole country. There were 21,457 patients with completed clinical data, biochemical indicators, physical examination, the Patient-Generated Subjective Global Assessment (PG-SGA) and Nutrition Risk Screening 2002 (NRS2002) survey. Logistic regression analysis was used to figure out the influencing factors of NLR, and four models were established to evaluate the influence of NLR on body functions, nutritional risks and nutritional status. Results: Male patients, TNM stage IV, total bilirubin, hypertension and coronary atherosclerotic heart disease (CAHD) were independent predictors of NLR >2.5. BMI, digestive systemic tumors and triglyceride negatively affect NLR in multivariable logistic regression. NLR was an independent predictor of Karnofsky Performance Scale (KPS), fat store deficit in all degrees, moderate and severe muscle deficit, mild fluid retention and PG-SGA grade. Conclusion: Male patients and those with hypertension and CAHD are prone to systemic inflammation. Systemic inflammation significantly degrades body function status and nutritional status, increases nutritional risk and influences fat and muscle metabolism in patients with malignant tumor. Improving the intervenable indicators such as elevating albumin and pre-albumin, decreasing total bilirubin and enhancing nutrition support are imperative. Obesity and triglyceride behave like anti-systemic inflammation, which is misleading due to reverse causation in the course of malignancy.

P53/miR-34a/SIRT1 positive feedback loop regulates the termination of liver regeneration.

BACKGROUND: The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury, cancer resection, or living donor liver transplantation. Only a few studies have shed light on the mechanisms involved in the termination stage of LR. Here, we attempt to further verify the role of the p53/miR-34a/SIRT1 positive feedback loop in the termination of liver regeneration and its possible relationship with liver cancer. METHOD: We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) overexpressing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. RESULTS: We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 or miR-34a terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. T-ß-MCA increased gradually during LR and peaked at 7 days after PH. T-ß-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. The P53/miR-34a/SIRT1 positive feedback loop was abolished in HCC patients with P53 mutations. CONCLUSIONS: The P53/miR-34a/SIRT1 positive feedback loop plays an important role in the termination of LR. Our findings showed the molecular and metabolic mechanisms of LR termination and provide a potential therapeutic alternative for treating P53-wild-type HCC patients.

FNBP4 is a Potential Biomarker Associated with Cuproptosis and Promotes Tumor Progression in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that lacks an efficient therapeutic approach because of its elusive molecular mechanisms. This study aimed to investigate the biological function and potential mechanism of formin-binding protein 4 (FNBP4) in HCC. Methods: FNBP4 expression in tissues and cells were detected by quantitative real-time PCR (qRT‒PCR), Western blot, and immunohistochemistry (IHC). The Kaplan-Meier method was used to explore the correlation between the FNBP4 expression and clinical survival. MTT, EdU incorporation, colony formation, and Transwell assays were performed to evaluate the function of FNBP4 in cell proliferation and migration in vitro. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to explore the potential mechanism of FNBP4. The prognostic risk signature and nomogram were constructed to demonstrate the prognostic value of FNBP4. Results: We found that FNBP4 was upregulated in patients with HCC and associated with poor overall survival (OS). Furthermore, knockdown of FNBP4 inhibited the proliferation and migration in HCC cells. Then, we performed a KEGG pathway analysis of the coexpressed genes associated with FNBP4 and found that FNBP4 may be associated with tumor-related signaling pathways and cuproptosis. We verified that FNBP4 could cause cell cycle progression and inactivation of the hippo signaling pathway. A prognostic risk signature containing three FNBP4-related differentially expressed cuproptosis regulators (DECRs) was established and can be used as an independent risk factor to evaluate the prognosis of patients with HCC. In addition, a nomogram including a risk score and clinicopathological factors was used to predict patient survival probabilities. Conclusion: FNBP4, as a potential biomarker associated with cuproptosis, promotes HCC cell proliferation and metastasis. We provide a new potential strategy for HCC treatment by targeting FNBP4.

Highly efficient acrylic acid production from formaldehyde and acetic acid over the NASICON-type catalyst.

The condensation of formaldehyde and acetic acid to acrylic acid (AA) is considered as one of the important routes for the clean and high value utilization of coal-based methanol derivatives. Herein, we successfully synthesized environment-friendly NASICON catalysts using Ti(SO4)2 as the titanium source. With guaranteed high selectivity (∼78%), the space time yield of AA + MA (methyl acrylate) can be up to 123.9 µmol g-1 min-1, far higher than the results reported previously. Based on the characterizations, it is demonstrated that the modulation of the acidic and basic properties (including distribution, ratio of B/L, etc.) led by the specific elemental and hybrid TiP2O7 phase plays crucial roles in catalyst supremacy.

BMSCs-Seeded Interpenetrating Network GelMA/SF Composite Hydrogel for Articular Cartilage Repair.

Because of limited self-healing ability, the treatment of articular cartilage defects is still an important clinical challenge. Hydrogel-based biomaterials have broad application prospects in articular cartilage repair. In this study, gelatin methacrylate (GelMA)and silk fibroin (SF) were combined to form a composite hydrogel with an interpenetrating network (IPN) structure under ultraviolet irradiation and ethanol treatment. Introducing silk fibroin into GelMA hydrogel significantly increased mechanical strength as compressive modulus reached 300 kPa in a GelMA/SF-5 (50 mg/mL silk fibroin) group. Moreover, composite IPN hydrogels demonstrated reduced swelling ratios and favorable biocompatibility and supported chondrogenesis of bone mesenchymal stem cells (BMSCs) at day 7 and day 14. Additionally, significantly higher gene expressions of Col-2, Acan, and Sox-9 (p < 0.01) were found in IPN hydrogel groups when compared with the GelMA group. An in vivo study was performed to confirm that the GelMA-SF IPN hydrogel could promote cartilage regeneration. The results showed partial regeneration of cartilage in groups treated with hydrogels only and satisfactory cartilage repair in groups of cell-seeded hydrogels, indicating the necessity of additional seeding cells in hydro-gel-based cartilage treatment. Therefore, our results suggest that the GelMA/SF IPN hydrogels may be a potential functional material in cartilage repair and regeneration.