FoxO3 Regulates Mouse Bone Mesenchymal Stem Cell Fate and Bone-Fat Balance During Skeletal Aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factor is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-polymerase chain reaction, Western blot, and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling, respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs and is a potential target for the prevention of age-related osteoporosis.

Transcriptomics analysis of LINC02202/XBP1 axis in melanoma: Implications for drug targeting and PD-1 monoclonal antibody efficacy.

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.

Reviving Zn0 Dendrites to Electroactive Zn2+ by Mesoporous MXene with Active Edge Sites.

Zinc metal-based aqueous batteries (ZABs) offer a sustainable, affordable, and safe energy storage alternative to lithium, yet inevitable dendrite formation impedes their wide use, especially under long-term and high-rate cycles. How the battery can survive after dendrite formation remains an open question. Here, we pivot from conventional Zn dendrite growth suppression strategies, introducing proactive dendrite-digesting chemistry via a mesoporous Ti3C2 MXene (MesoTi3C2)-wrapped polypropylene separator. Spectroscopic characterizations and electrochemical evaluation demonstrate that MesoTi3C2, acting as an oxidant, can revive the formed dead Zn0 dendrites into electroactive Zn2+ ions through a spontaneous redox process. Density functional theory reveals that the abundant edge-Ti-O sites in our MesoTi3C2 facilitate high oxidizability and electron transfer from Zn0 dendrites compared to their in-plane counterparts. The resultant asymmetrical cell demonstrates remarkable ultralong cycle life of 2200 h at a practical current of 5 mA cm-2 with a low overpotential (<50 mV). The study reveals the unexpected edge effect of mesoporous MXenes and uncovers a new proactive dendrite-digesting chemistry to survive ZABs, albeit with inevitable dendrite formation.

PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects.

BACKGROUND: One of the common adverse reactions in patients with pressure ulcers (PU) is sepsis, which is mainly related to microbial infections caused by pathogenic organisms. The activation of nuclear factor kappa-B (NF-κB) frequently occurs in conjunction with pathogenic microbial infections. Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is closely related to inflammatory disorders. The role and mechanism of PSTPIP2 in sepsis because of pressure ulcers is unclear. In this study, we discovered that PSTPIP2 was lowly expressed in peripheral blood of patients with sepsis induced by pressure ulcers. METHODS: Peripheral blood was collected from 20 patients with sepsis due to pressure ulcers and 10 healthy controls, and the expression of PSTPIP2 in peripheral blood was discovered by polymerase chain reaction and Western blot analysis. Information on the clinical characteristics of patients was summarized, and the expression data of PSTPIP2 were correlated with the patients' acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C-reactive protein (CRP) and procalcitonin (PCT) scores by Spearman's correlation analysis. One of the main mediators of Gram-negative sepsis is lipopolysaccharide (LPS). In order to establish an in vitro sepsis model, THP-1 cells were treated with LPS, and the cells were transfected with PSTPIP2. Contents of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in each group of cells were detected by enzyme-linked--immunosorbent serologic assay, and NF-κB-related proteins were detected by Western blot analysis. RESULTS: When compared to healthy controls, the peripheral blood of patients with pressure sepsis had lower PSTPIP2 expression, which had a negative correlation with the APACHE II, SOFA, CRP, and PCT scores. LPS-induced THP-1 cells expressed less PSTPIP2 than the untreated control cells, and PSTPIP2 transfection decreased IL-6, IL-1ß, and TNF-α levels and inhibited the activation of NF-κB pathway. CONCLUSION: PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects.

Hsa_circ_0005085 may suppress cutaneous squamous cell carcinoma growth and metastasis through targeting the miR-186-5p/LAMC1 axis.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from the skin. Mounting evidence suggests that circular RNAs (circRNAs) participate in diverse biological functions in human cancers, containing CSCC. However, the biological functions and underlying mechanism of hsa_circ_0005085 in CSCC have not been clearly studied. METHODS: Expression levels of hsa_circ_0005085, microRNA-186-5p (miR-186-5p), and Laminin subunit gamma 1 (LAMC1) were detected by reverse transcription-quantitative polymerase chain reaction. Cell counting kit-8 assay, colony formation assay, and 5-Ethynyl-2'-deoxyuridine assay were used to assess cell proliferation. Transwell assay was conducted to detect cell migration and invasion. Cell apoptosis was analyzed by flow cytometry. Protein expression of LAMC1, E-cadherin, Snail, and slug were assessed using western blot assay. Using bioinformatics software, the binding between miR-186-5p and hsa_circ_0005085 or LAMC1 was predicted, followed by verification using a dual-luciferase reporter and RNA-Immunoprecipitation. The mouse xenograft model was established to investigate the role of hsa_circ_0005085 in vivo. RESULTS: Hsa_circ_0005085 level was downregulated in CSCC tissues and cells. Overexpression of hsa_circ_0005085 inhibited cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in CSCC. MiR-186-5p could restore the effect of hsa_circ_0005085 overexpression on CSCC cells, and the knockdown of LAMC1 reversed the regulation of the miR-186-5p inhibitor. In mechanism, hsa_circ_0005085 served as a sponge for miR-186-5p to regulate LAMC1 expression. Overexpression of hsa_circ_0005085 reduced growth of tumor via miR-186-5p/LAMC1 axis in vivo. CONCLUSION: In our study, hsa_circ_0005085 might inhibit CSCC development by targeting the miR-186-5p/LAMC1 axis, which might provide a promising therapeutic target for CSCC.

Epidemiological Features of Klebsiella pneumoniae Infection in the Hepatobiliary System of Patients in Yantai, China, Based on Clinical and Genetic Analyses.

Purpose: To investigate the epidemiological features of Klebsiella pneumoniae infection of the hepatobiliary system of patients in Yantai, China. Methods: This retrospective study was conducted from January to December 2019 in Yantai Yuhuangding Hospital. Patients for whom K. pneumoniae was isolated from the hepatobiliary system were considered for inclusion. The clinical features and genetic analyses were conducted to explore the epidemiological characteristics. Results: A total of 88 cases were enrolled, including 69 cases of hypervirulent K. pneumoniae (hvKP) and 19 cases of classical K. pneumoniae (cKP). Community-acquired infections, fever, liver abscess, and C-reactive protein (CRP) and procalcitonin (PCT) levels were significantly higher, while biliary tract disease was lower in the hvKP group compared with the cKP group. Among the 69 hvKP infections, 61 developed a liver abscess. Community-acquired infections, fever, and CRP and PCT levels were higher, whereas biliary tract disease and malignancy were lower in the liver abscess group compared with the non-liver abscess group. All strains were susceptible to the majority of antibiotics tested. All hvKP strains possessed the bla SHV, oqxA, oqxB and fosA resistance genes. K1 and K2 accounted for 78% of hvKP strains. K1 strains belonged to sequence types ST23 and ST700, whereas K2 strains belonged to ST65, ST86 and ST5212. K1 isolates possessed the most virulence determinants, followed by K2 and non-K1/K2 isolates. K2 isolates lacked the allS gene, which was rare in non K1/K2 isolates, but present in most K1 isolates. The mceG gene was only detected in K1 isolates. AllS and virulence determinants were significantly more prevalent in the liver abscess group than in the non-liver abscess group. Conclusion: The prevalence of hvKP among K. pneumoniae infections of the hepatobiliary system is high in Yantai, China. Greater vigilance of hvKP infection is required in clinical and microbiological laboratories.

Ultrasensitive Chemiresistive Gas Sensor Can Diagnose Asthma and Monitor Its Severity by Analyzing Its Biomarker H2S: An Experimental, Clinical, and Theoretical Study.

Asthma is a chronic disease characterized by recurrent attacks of breathlessness and wheezing, which vary in severity and frequency from person to person. H2S is considered as the biomarker of asthma. Here, an ultrasensitive chemiresistive H2S gas sensor based on a γ-Bi2MoO6-CuO heterostructure with a detection limit of 5 ppb has been fabricated. It can distinguish asthmatic patients from healthy people roughly by analyzing the exhaled breaths of 28 asthmatic patients and 28 healthy people, suggesting that the sensor can be used to assist physicians in the diagnosis of asthma. Pathologically, it is discovered by this sensor that with the relief of asthma, the concentration of H2S in one's exhaled breath gradually increases. This subtle concentration variation of H2S can be accurately detected, indicating that this sensor can be used in the asthma severity monitoring too. Physical models have been built by first-principles calculation to reveal the causes of the sensor's ultrasensitivity. The stable adsorption of H2S on the surface of CuO results in massive charge transferring and the appearance of the defect states, which play the major role in the ultrasensitivity of the sensor. Upon integrating this sensor with circuits, the cheap, smart, and portable H2S sensing device can be obtained, which can make asthmatic patients' access to this device easy and make the severity monitoring of asthma convenient, especially for children and the aged.

Predictive Factors Associated With Short-Term Clinical Outcomes and Time to Return to Activity After Arthroscopic Partial Meniscectomy in Nonathletes.

Background: Although arthroscopic partial meniscectomy is a widely implemented surgical procedure, studies investigating the time to return to activity (RTA) are rare. Purpose: To explore which factors are associated with the RTA times after arthroscopic partial meniscectomy and to investigate whether those factors can also improve short-term patient-reported outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: The authors reviewed the records of patients who underwent isolated partial meniscectomy in their institution from January 2017 to December 2019. Patient and injury characteristics were documented, and time to RTA was obtained via phone interview in January 2021. Pre- and postoperative outcomes were assessed with the Lysholm score and International Knee Documentation Committee (IKDC) score. The chi-square test and independent-samples t test were used to evaluate differences in outcome scores and time to RTA according to the patient and injury characteristics, and risk factors with a P value <.1 in the univariate analysis were used in the binary regression. Results: Included were 215 patients (87 men and 128 women; mean age, 33.7 years [range, 24-75 years]). Of these patients, 204 provided information on time to RTA (mean, 3.3 months). By 3 months postoperatively, 49.5% (101/204) of patients could perform activities without knee-related restriction; this improved to 69.6% (142/204) at 6 months and 90.2% (184/204) at 12 months. On multivariate logistic regression analysis, age (OR, 0.39; 95% CI, 0.21-1.19; P = .044) and injury duration (OR, 0.20; 95% CI, 0.19-1.07; P = .032) were significantly associated with the time to RTA. IKDC scores improved significantly from 41.2 preoperatively to 76.7 postoperatively, and in the multivariate logistic regression model, female sex (OR, 2.67; 95% CI, 1.10-6.47; P = .030), body mass index (BMI) ≥27 kg/m2 (OR, 2.96; 95% CI, 1.02-8.66; P = .047), and medial meniscal tear (OR, 0.20; 95% CI, 0.04-1.00; P = .050) were associated with inferior outcome scores. Conclusion: Patients aged 40 years and younger who underwent partial meniscectomy surgery within 6 months after a meniscal tear were more likely to have a shorter time to RTA, and female patients with obesity (BMI ≥27 kg/m2), especially those with medial meniscal tears, tended to have inferior clinical outcomes.

Novel CaMKII-δ Inhibitor Hesperadin Exerts Dual Functions to Ameliorate Cardiac Ischemia/Reperfusion Injury and Inhibit Tumor Growth.

BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca2+/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart. METHODS: A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell-derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin. RESULTS: Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9-induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell-derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury. CONCLUSIONS: Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.

Mutations and clinical significance of calcium voltage-gated channel subunit alpha 1E (CACNA1E) in non-small cell lung cancer.

CACNA1E is a gene encoding the ion-conducting α1 subunit of R-type voltage-dependent calcium channels, whose roles in tumorigenesis remain to be determined. We previously showed that CACNA1E was significantly mutated in patients with non-small cell lung cancer (NSCLC) who were long-term exposed to household air pollution, with a mutation rate of 19% (15 of 79 cases). Here we showed that CACNA1E was also mutated in 207 (12.8%) of the 1616 patients with NSCLC in The Cancer Genome Atlas (TCGA) datasets. At mRNA and protein levels, CACNA1E was elevated in tumor tissues compared to counterpart non-tumoral lung tissues in NSCLCs of the public datasets and our settings, and its expression level was inversely associated with clinical outcome of the patients. Overexpression of wild type (WT) or A275S or R249G mutant CACNA1E transcripts promoted NSCLC cell proliferation with activation of epidermal growth factor receptor (EGFR) signaling pathway, whereas knockdown of this gene exerted inhibitory effects on NSCLC cells in vitro and in vivo. CACNA1E increased current density and Ca2+ entrance, whereas calcium channel blockers inhibited NSCLC cell proliferation. These data indicate that CACNA1E is required for NSCLC cell proliferation, and blockade of this oncoprotein may have therapeutic potentials for this deadly disease.

Circular RNA circ-LARP1B contributes to cutaneous squamous cell carcinoma progression by targeting microRNA-515-5p/TPX2 microtubule nucleation factor axis.

Circular RNAs (circRNAs) have shown pivotal regulatory roles in tumorigenesis and progression. Our purpose was to analyze the role of circRNA La ribonucleoprotein 1B (circ-LARP1B; hsa_circ_0070934) in cutaneous squamous cell carcinoma (CSCC) progression and its associated mechanism. Cell viability, colony formation ability, migration, and invasion were analyzed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound healing assay, and transwell invasion assay. Flow cytometry was performed to analyze cell apoptosis and cell cycle progression. Cell glycolytic metabolism was analyzed using Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II, and ATP colorimetric Assay kit. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the interaction between microRNA-515-5p (miR-515-5p) and circ-LARP1B or TPX2 microtubule nucleation factor (TPX2). Circ-LARP1B expression was up-regulated in CSCC tissues and cell lines. Circ-LARP1B knockdown suppressed cell viability, colony formation ability, migration, invasion, cell cycle progression, and glycolysis and triggered cell apoptosis in CSCC cells. miR-515-5p was a direct target of circ-LARP1B in CSCC cells, and circ-LARP1B silencing-mediated anti-tumor effects were largely counteracted by miR-515-5p knockdown. miR-515-5p directly interacted with the 3' untranslated region (3'UTR) of TPX2. TPX2 overexpression largely overturned miR-515-5p-mediated anti-tumor effects in CSCC cells. Circ-LARP1B could up-regulate TPX2 expression by sponging miR-515-5p in CSCC cells. Circ-LARP1B knockdown suppressed tumor growth in vivo. In conclusion, circ-LARP1B contributed to CSCC progression by targeting miR-515-5p/TPX2 axis. The circ-LARP1B/miR-515-5p/TPX2 axis might provide novel therapeutic targets for CSCC patients.

miR-433-3p Targets AJUBA to Inhibit Malignant Progression of Glioma.

INTRODUCTION: Glioma is the most aggressive and malignant type of tumors among primary intracranial tumors. miR-433-3p has been verified to be correlated with the formation and progression of many types of cancers. METHODS: In this study, the effects of miR-433-3p and AJUBA on the proliferation, migration, and invasion of glioma and the molecular mechanisms were investigated. We analyzed bioinformatics databases and conducted cell biology experiments to determine that compared with adjacent tissue and normal cells, the expression level of miR-433-3p in glioma tissue and cells was lower, while the expression level of AJUBA was higher. Overexpressing miR-433-3p could significantly inhibit the proliferation, migration, and invasion of glioma cells and promote cell apoptosis. RESULTS: In addition, after overexpressing miR-433-3p and AJUBA, it was found that overexpressing AJUBA could attenuate the inhibitory effect of overexpressing miR-433-3p on the proliferation, migration, and invasion of glioma cells, which suggested that miR-433-3p regulated the biological function of glioma by downregulating AJUBA expression. CONCLUSION: These results proved that miR-433-3p could target to inhibit the expression of AJUBA, thus inhibiting the biological function and malignant progression of glioma.

Bone Marrow Adipocytes: A Critical Player in the Bone Marrow Microenvironment.

Recognized for nearly 100 years, bone marrow adipocytes (BMAs) form bone marrow niches that contain hematopoietic and bone cells, the roles of which have long been underestimated. Distinct from canonical white, brown, and beige adipocytes, BMAs derived from bone marrow mesenchymal stromal cells possess unique characteristics and functions. Recent single-cell sequencing studies have revealed the differentiation pathway, and seminal works support the tenet that BMAs are critical regulators in hematopoiesis, osteogenesis, and osteoclastogenesis. In this review, we discuss the origin and differentiation of BMAs, as well as the roles of BMAs in hematopoiesis, osteogenesis, osteoclastogenesis, and immune regulation. Overall, BMAs represent a novel target for bone marrow-related diseases, including osteoporosis and leukemia.

Hidden blood loss in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgery: a retrospective study of 765 cases at a single centre.

BACKGROUND: In scoliosis corrective surgery, total blood loss is composed of visible blood loss, including intraoperative haemorrhage and drainage, and hidden blood loss in which blood extravasates into the tissues and accumulates in the surgical field. The purpose of this study was to investigate hidden blood loss (HBL) and its potential risk factors in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgery and elucidate the influence of HBL on the necessity for postoperative blood transfusion. METHODS: We retrospectively studied adolescent idiopathic scoliosis patients undergoing posterior spine fusion for adolescent idiopathic scoliosis from January 2014 to December 2018 at our hospital. The patients' demographics, blood loss-related parameters, surgeries and blood loss data were extracted. The association between patient characteristics and HBL was analyzed by Pearson or Spearman correlation analyses. Multivariate linear regression analysis was used to determine independent risk factors associated with HBL. Binary logistic regression analysis was used to analyze the influence of HBL on the necessity for postoperative blood transfusion. RESULTS: A total of 765 patients, of whom 128 were male and 637 were female (age range 10-18 years), were included in this study. The mean volume of HBL was 693.5 ± 473.4 ml, accounting for 53.9 % of the total blood loss. The multivariate linear regression analysis revealed that preoperative Hct (p = 0.003) and allogeneic blood transfusion (p < 0.001) were independent risk factors for HBL, while tranexamic acid (p = 0.003) was negatively correlated with HBL. Binary logistic regression analysis showed that HBL > 850 ml (P < 0.001, OR: 8.845, 95 % CI: 5.806-13.290) was an independent risk factor for the necessity for postoperative blood transfusion. CONCLUSIONS: Substantial HBL occurred in adolescent idiopathic scoliosis patients undergoing posterior spinal fusion surgeries. Allogeneic blood transfusion and preoperative Hct were independent risk factors for HBL, while tranexamic acid was negatively related to HBL. HBL and its influencing factors should be considered when planning perioperative transfusion management. Patients with HBL greater than 850 ml should be closely monitored in cases of postoperative anaemia. LEVEL OF EVIDENCE: Level III.

RANKL from bone marrow adipose lineage cells promotes osteoclast formation and bone loss.

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclast formation and bone remodeling. Nevertheless, the cellular source of RANKL for osteoclastogenesis has not been fully uncovered. Different from peripheral adipose tissue, bone marrow (BM) adipose lineage cells originate from bone marrow mesenchymal stromal cells (BMSCs). Here, we demonstrate that adiponectin promoter-driven Cre expression (AdipoqCre ) can target bone marrow adipose lineage cells. We cross the AdipoqCre mice with ranklfl/fl mice to conditionally delete RANKL from BM adipose lineage cells. Conditional deletion of RANKL increases cancellous bone mass of long bones in mice by reducing the formation of trabecular osteoclasts and inhibiting bone resorption but does not affect cortical bone thickness or resorption of calcified cartilage. AdipoqCre ; ranklfl/fl mice exhibit resistance to estrogen deficiency and rosiglitazone (ROS)-induced trabecular bone loss but show bone loss induced by unloading. BM adipose lineage cells therefore represent an essential source of RANKL for the formation of trabecula osteoclasts and resorption of cancellous bone during remodeling under physiological and pathological conditions. Targeting bone marrow adiposity is a promising way of preventing pathological bone loss.

Rationalizing the promotional effect of Mn oxides in benzene combustion using an O 2p-band center descriptor.

Our work sheds light on using the O 2p-band center as a useful electronic descriptor for understanding the variations in catalytic reducibility of transition metal oxides (TMOs) and the promotional effect of MnO2 during catalytic benzene combustion. The "volcano"-type activity plot, in conjunction with the reduction characteristic of the TMOs, ultimately reflects the Sabatier principle, which states that a good catalyst (i.e., MnO2) balances the capability of oxygen abstraction and uptake in the case of benzene combustion.

A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model.

Oncolytic viruses (OV) have shown excellent safety and efficacy in preclinical and clinical studies. Influenza A virus (IAV) is considered a promising oncolytic virus. In this report, we generated a recombinant influenza virus expressing an immune checkpoint blockade agent targeting CTLA4. Using reverse genetics, a recombinant influenza virus, termed rFlu-CTLA4, encoding the heavy chain of a CTLA4 antibody on the PB1 segment and the light chain of the CTLA4 antibody on the PA segment was produced. RFlu-CTLA4 could replicate to high titers, and antibodies were produced in the allantoic fluid of infected eggs. Furthermore, the selective cytotoxicity of the virus was higher in various hepatocellular carcinoma cancer cell lines than in the normal cell line L02 in vitro, as indicated by MTS assays. More importantly, in a subcutaneous H22 mouse hepatocarcinoma model, intratumoral injections of rFlu-CTLA4 inhibited the growth of treated tumors and increased the overall survival of mice compared with injections of the PR8 virus. Taken together, these results warrant further exploration of this novel recombinant influenza virus for its potential use as a single or combination agent for cancer immunotherapy.

Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation.

Bone marrow mesenchymal stromal cells (BMSCs), identified as pericytes comprising the hematopoietic niche, are a group of heterogeneous cells composed of multipotent stem cells, including osteochondral and adipocyte progenitors. Nevertheless, the identification and classification are still controversial, which limits their application. In recent years, by lineage tracing and single-cell sequencing, several new subgroups of BMSCs and their roles in normal physiological and pathological conditions have been clarified. Key regulators and mechanisms controlling the fate of BMSCs are being revealed. Cross-talk among subgroups of bone marrow mesenchymal cells has been demonstrated. In this review, we focus on recent advances in the identification and classification of BMSCs, which provides important implications for clinical applications.

Endoscopic submucosal dissection versus esophagectomy for early esophageal squamous cell carcinoma with tumor invasion to different depths.

Endoscopic submucosal dissection (ESD) is a minimally invasive alternative to esophagectomy for early esophageal squamous cell carcinoma (EESCC). The aim of this study was to compare the efficacy and safety of ESD and esophagectomy in EESCC with different depth of invasion. The data of EESCC patients who received ESD or esophagectomy between Jan 2011 to Dec 2018 at our center were retrospectively analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy patients. 222 EESCC patients underwent ESD, while 184 underwent esophagectomy. No significant differences were found between the two groups in OS (P=0.417), DSS (P=0.423), and RFS (P=0.726). Procedure duration, post-procedure hospital stay, and hospitalization cost were all lower in ESD patients. Oncologic outcomes were similar between the two groups in propensity score-matched analysis. The R0 resection rate was comparable between ESD and esophagectomy groups in the T1a-M1/M2 and M3/SM1 EESCC subgroups; no significant differences were found in OS, DSS and RFS. In the SM2/SM3 EESCC subgroup, although the prognosis of the two treatment groups was similar, the R0 resection rate was significantly lower in ESD patients than in esophagectomy patients. Thus, we concluded ESD could be a first-line treatment for T1a-M1/M2 and M3/SM1 EESCC as oncologic outcome is comparable to that achieved with esophagectomy with minimal invasion, lower cost and lower incidence of serious adverse events. However, in SM2/SM3 EESCC patients, esophagectomy may be preferable.

Effects of early oral feeding after radical total gastrectomy in gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is a heavy burden in China. Nutritional support for GC patients is closely related to postoperative rehabilitation. However, the role of early oral feeding after laparoscopic radical total gastrectomy in GC patients is unclear and high-quality research evidence is scarce. AIM: To prospectively explore the safety, feasibility and short-term clinical outcomes of early oral feeding after laparoscopic radical total gastrectomy for GC patients. METHODS: This study was a prospective cohort study conducted between January 2018 and December 2019 based in a high-volume tertiary hospital in China. A total of 206 patients who underwent laparoscopic radical total gastrectomy for GC were enrolled. Of which, 105 patients were given early oral feeding (EOF group) after surgery, and the other 101 patients were given the traditional feeding strategy (control group) after surgery. Perioperative clinical data were recorded and analyzed. The primary endpoints were gastrointestinal function recovery time and postoperative complications, and the secondary endpoints were postoperative nutritional status, length of hospital stay and expenses, etc. RESULTS: Compared with the control group, patients in the EOF group had a significantly shorter postoperative first exhaust time (2.48 ± 1.17 d vs 3.37 ± 1.42 d, P = 0.001) and first defecation time (3.83 ± 2.41 d vs 5.32 ± 2.70 d, P = 0. 004). In addition, the EOF group had a significant shorter postoperative hospitalization duration (5.85 ± 1.53 d vs 7.71 ± 1.56 d, P < 0.001) and lower postoperative hospitalization expenses (16.60 ± 5.10 K¥ vs 21.00 ± 7.50 K¥, P = 0.014). On the 5th day after surgery, serum prealbumin level (214.52 ± 22.47 mg/L vs 204.17 ± 20.62 mg/L, P = 0.018), serum gastrin level (246.30 ± 57.10 ng/L vs 223.60 ± 55.70 ng/L, P = 0.001) and serum motilin level (424.60 ± 68.30 ng/L vs 409.30 ± 61.70 ng/L, P = 0.002) were higher in the EOF group. However, there was no significant difference in the incidence of total postoperative complications between the two groups (P = 0.507). CONCLUSION: Early oral feeding after laparoscopic radical total gastrectomy can promote the recovery of gastrointestinal function, improve postoperative nutritional status, reduce length of hospital stay and expenses while not increasing the incidence of related complications, which indicates its safety, feasibility and potential benefits for gastric cancer patients.