Personalized neoantigen vaccine enhances the therapeutic efficacy of bevacizumab and anti-PD-1 antibody in advanced non-small cell lung cancer.

Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.

Structure-Guided Discovery of Diverse Cytotoxic Dimeric Xanthones/Chromanones from Penicillium chrysogenum C-7-2-1 and Their Interconversion Properties.

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new (1-14) and 6 known tetrahydroxanthone chromanone homo- and heterodimers (15-20) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5, 7, 8, and 16 exhibited significant cytotoxicity against H23 cell line with IC50 values of 6.9, 6.4, 3.9, and 2.6 µM, respectively.

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound.

Pharmacological treatment of gliomas and other brain-infiltrating tumors remains challenging due to limited delivery of most therapeutics across the blood-brain barrier (BBB). Transcranial MRI-guided focused ultrasound (FUS), an emerging technology for noninvasive brain treatments, enables transient opening of the BBB through acoustic activation of circulating microbubbles. Here, we evaluate the safety and utility of transcranial microbubble-enhanced FUS (MB-FUS) for spatially targeted BBB opening in patients with infiltrating gliomas. In this Phase 0 clinical trial (NCT03322813), we conducted comparative and quantitative analyses of FUS exposures (sonications) and their effects on gliomas using MRI, histopathology, microbubble acoustic emissions (harmonic dose [HD]), and fluorescence-guided surgery metrics. Contrast-enhanced MRI and histopathology indicated safe and reproducible BBB opening in all patients. These observations occurred using a power cycling closed feedback loop controller, with the power varying by nearly an order of magnitude on average. This range underscores the need for monitoring and titrating the exposure on a patient-by-patient basis. We found a positive correlation between microbubble acoustic emissions (HD) and MR-evident BBB opening (P = 0.07) and associated interstitial changes (P < 0.01), demonstrating the unique capability to titrate the MB-FUS effects in gliomas. Importantly, we identified a 2.2-fold increase of fluorescein accumulation in MB-FUS-treated compared to untreated nonenhancing tumor tissues (P < 0.01) while accounting for vascular density. Collectively, this study demonstrates the capabilities of MB-FUS for safe, localized, controlled BBB opening and highlights the potential of this technology to improve the surgical and pharmacologic treatment of brain tumors.

Bulk and single-cell characterisation of the immune heterogeneity of atherosclerosis identifies novel targets for immunotherapy.

BACKGROUND: Immune cells that infiltrate lesions are important for atherosclerosis progression and immunotherapies. This study was aimed at gaining important new insights into the heterogeneity of these cells by integrating the sequencing results of multiple samples and using an enhanced single-cell sequencing workflow to overcome the limitations of a single study. RESULTS: Integrative analyses identified 28 distinct subpopulations based on gene expression profiles. Further analysis demonstrated that these cells manifested high heterogeneity at the levels of tissue preferences, genetic perturbations, functional variations, immune dynamics, transcriptional regulators, metabolic changes, and communication patterns. Of the T cells, interferon-induced CD8+ T cells were involved in the progression of atherosclerosis. In contrast, proinflammatory CD4+ CD28null T cells predicted a poor outcome in atherosclerosis. Notably, we identified two subpopulations of foamy macrophages that exhibit contrasting phenotypes. Among them, TREM2- SPP1+ foamy macrophages were preferentially distributed in the hypoxic core of plaques. These glycolytic metabolism-enriched cells, with impaired cholesterol metabolism and robust pro-angiogenic capacity, were phenotypically regulated by CSF1 secreted by co-localised mast cells. Moreover, combined with deconvolution of the bulk datasets, we revealed that these dysfunctional cells had a higher proportion of ruptured and haemorrhagic lesions and were significantly associated with poor atherosclerosis prognoses. CONCLUSIONS: We systematically explored atherosclerotic immune heterogeneity and identified cell populations underlying atherosclerosis progression and poor prognosis, which may be valuable for developing new and precise immunotherapies.

Research progress on metal-organic framework compounds (MOFs) in electrocatalysis.

Metal-organic frameworks (MOFs) have favorable characteristics such as large specific surface area, high porosity, structural diversity, and pore surface modification, giving them great potential for development and attractive prospects in the research area of modern materials electrocatalysis. However, unsatisfactory catalytic activity and poor electronic conductivity are the main challenges facing MOFs. This review focuses on MOF-based materials used in electrocatalysis, based on the types of catalytic reactions that have used MOF-based materials in recent years along with their applications, and also looks at some new electrocatalytic materials and their future development prospects.

Effects of diabetes mellitus and glycemic traits on cardiovascular morpho-functional phenotypes.

BACKGROUND: The effects of diabetes on the cardiac and aortic structure and function remain unclear. Detecting and intervening these variations early is crucial for the prevention and management of complications. Cardiovascular magnetic resonance imaging-derived traits are established endophenotypes and serve as precise, early-detection, noninvasive clinical risk biomarkers. We conducted a Mendelian randomization (MR) study to examine the association between two types of diabetes, four glycemic traits, and preclinical endophenotypes of cardiac and aortic structure and function. METHODS: Independent genetic variants significantly associated with type 1 diabetes, type 2 diabetes, fasting insulin (FIns), fasting glucose (FGlu), 2 h-glucose post-challenge (2hGlu), and glycated hemoglobin (HbA1c) were selected as instrumental variables. The 96 cardiovascular magnetic resonance imaging traits came from six independent genome-wide association studies. These traits serve as preclinical endophenotypes and offer an early indication of the structure and function of the four cardiac chambers and two aortic sections. The primary analysis was performed using MR with the inverse-variance weighted method. Confirmation was achieved through Steiger filtering and testing to determine the causal direction. Sensitivity analyses were conducted using the weighted median, MR-Egger, and MR-PRESSO methods. Additionally, multivariable MR was used to adjust for potential effects associated with body mass index. RESULTS: Genetic susceptibility to type 1 diabetes was associated with increased ascending aortic distensibility. Conversely, type 2 diabetes showed a correlation with a reduced diameter and areas of the ascending aorta, as well as decreased distensibility of the descending aorta. Genetically predicted higher levels of FGlu and HbA1c were correlated with a decrease in diameter and areas of the ascending aorta. Furthermore, higher 2hGlu levels predominantly showed association with a reduced diameter of both the ascending and descending aorta. Higher FIns levels corresponded to increased regional myocardial-wall thicknesses at end-diastole, global myocardial-wall thickness at end-diastole, and regional peak circumferential strain of the left ventricle. CONCLUSIONS: This study provides evidence that diabetes and glycemic traits have a causal relationship with cardiac and aortic structural and functional remodeling, highlighting the importance of intensive glucose-lowering for primary prevention of cardiovascular diseases.

The Effects of MicroRNAs in the Development of Heart Failure.

PURPOSE OF REVIEW: Heart failure is a severe clinical syndrome with complex and unclarified mechanisms, and it poses a serious threat to human health. MicroRNA, a non-coding RNA, can directly bind to target genes and regulate their expression. The important role of microRNAs in the development of HF has become a hot topic of research in recent years. This paper summarizes and prospects the mechanisms of microRNAs in regulating cardiac remodeling during heart failure to provide reference ideas for further research and clinical treatment. RECENT FINDINGS: With extensive research, more target genes for microRNAs have been clarified. By modulating various molecules, microRNAs affect the contractile function of the myocardium and alter the process of myocardial hypertrophy, myocyte loss, and fibrosis, thereby interfering with the process of cardiac remodeling and exerting an important effect in the process of heart failure. Based on the above mechanism, microRNAs have promising applications in the diagnosis and treatment of heart failure. MicroRNAs form a complex post-transcriptional control mechanism of gene expression, and the increase or decrease of their content during heart failure largely alters the course of cardiac remodeling. By continuously identifying their target genes, it is expected to achieve more precise diagnosis and treatment of this important topic of heart failure.

Relationship of matrix stiffness and cell morphology in regulation of osteogenesis and adipogenesis of BMSCs.

BACKGROUNDS: Matrix stiffness has been found to regulate cell morphology, while both cell morphology and matrix stiffness are verified as important factors directing BMSCs (bone marrow mesenchymal stem cells) differentiation. This study aimed to investigate whether matrix stiffness depended on cell morphology to regulate osteogenesis and adipogenesis of BMSCs on 2D substrates. METHODS AND RESULTS: First, we seeded BMSCs on tissue culture plates (TCPs) with different fibronectin (FN) concentrations and cytoskeleton inhibitor cytochalasin D, and FN was found to promote cell spreading and osteogenesis while inhibiting adipogenesis of BMSCs through F-actin reorganization. Based on these, we modulated BMSCs morphology on 0.5 kPa and 32 kPa CytoSoft® substrates through FN. High concentration of FN (300 µg/ml) coated on 0.5 kPa substrates promoted cell spreading to similar levels with 32 kPa substrates coated with 100 µg/ml of FN, and cells in both groups dominantly commit osteogenesis. On the other hand, low FN concentration (30 µg/ml) on 32 kPa substrates induced restricted cell morphology similar with 0.5 kPa substrates coated with 100 µg/ml of FN, and cells in both groups mainly commit adipogenesis. Immunofluorescence indicated nuclear translocation and higher intensity of YAP/TAZ when cells spread to larger areas, regardless of matrix stiffness. However, when cell spreading areas were fixed as similar levels, matrix stiffness didn't significantly affect YAP/TAZ intensity or location. CONCLUSIONS: Matrix stiffness failed to regulate BMSCs differentiation and YAP/TAZ activity without corresponding cell morphology. Cell spreading area could mediate effects of matrix stiffness on osteogenesis and adipogenesis of BMSCs.

Seasonal variation of heavy metals in suspended sediments downstream the Three Gorges Dam in the Yangtze River.

High sediment flux in large rivers provide sufficient dilution to the heavy metals' concentration. However, sediment starvation caused by hydrological engineering in recent decades has been reported worldwide. Thus, a study is necessary on the influences of recent declining sediment flux on heavy metal pollution change in the suspended sediments. In this study, heavy metal concentrations and speciation (Cd, Pb, Zn, Cu, Co, Ni, and Cr) in suspended sediments were investigated downstream the Three Gorges Dam (TGD) during dry and flood seasons. Substantial changes of Pb, Zn, Cd, and Cu along the river channel were found which were constrained by the dilution efficiency of suspended sediment during the dry season. High proportion of labile fraction revealed anthropogenic sources of heavy metal. Moreover, the historical trend of metal content illustrated TGD construction together with anthropogenic influx both contribute to the increasing environmental risk in the Yangtze River basin.

Effects of biophysical cues of 3D hydrogels on mesenchymal stem cells differentiation.

For stem cell research, three-dimensional (3D) hydrogels are increasingly recognized as more physiological systems than two-dimensional culture plates due to bidirectional and 3D interaction of stem cells and surrounding matrix. Among various stem cells, mesenchymal stem cells (MSCs) are one of the most widely applied from bench to bedside. In 3D hydrogels, MSCs are allowed to actively remodel the surrounding matrix through proteolytic degradation and cell-exerted force, which highly resembles in vivo situation. Notably, factors affecting hydrogel modifiability including matrix viscoelasticity and matrix degradability have been found to regulate adhesion, morphology, and fate decision of MSCs. In addition, MSCs within 3D hydrogels have been found to employ multiple mechanotransduction mechanisms including not only the classic integrin-actomyosin cytoskeleton system but also ion channels, microtubule cytoskeleton, and self-secreted proteinaceous matrix. This review summarizes the effects of biophysical cues on MSCs differentiation in 3D hydrogels and underlying mechanobiology in a hope to update our readers' understanding of stem cell biology and guide tissue engineering.

The value of glycosylated hemoglobin in the diagnosis of diabetic retinopathy: a systematic review and Meta-analysis.

OBJECTIVE: Glycosylated hemoglobin (HbA1c) has obvious clinical value in the diagnosis of diabetes, but the conclusions on the diagnostic value of diabetic retinopathy (DR) are not consistent. This study aims to comprehensively evaluate the accuracy of glycosylated hemoglobin in the diagnosis of diabetic retinopathy through the meta-analysis of diagnostic tests. METHODS: Cochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Wanfang Database, Chinese Biomedical Literature Database (CBM) were searched until November, 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and areas under the receiver operating characteristic (ROC) curve were calculated by Stata 15.0 software. RESULTS: After screening, 18 high-quality papers were included. The results of meta-analysis showed that the combined DOR = 18.19 (95% CI: 10.99-30.11), the sensitivity= 0.81 (95% CI): 0.75 ~ 0.87), specificity = 0.81 (95%CI: 0.72 ~ 0.87), +LR = 4.2 (95%CI: 2.95 ~ 6.00), -LR = 0.23 (95%CI: 0.17 ~ 0.31), and the area under the Summary ROC curve was 0.88 (95%CI: 0.85 ~ 0.90). CONCLUSION: The overall accuracy of HbA1cC forin diagnosing diabetic retinopathy is good. As it is more stable than blood sugar and is not affected by meals, it may be a suitable indicator for diabetic retinopathy.

Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China.

OBJECTIVE: To investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA. METHODS: A prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018. RESULTS: Of the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients' blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups. CONCLUSION: It is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.

Study of stability and interference for catecholamines and metanephrines, 3-methoxytyramine: key point of an accurate diagnosis for pheochromocytoma and paraganglioma.

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.

Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption.

Blood-brain/blood-tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs. <20 µm and 42 ± 7 vs. 12 ± 4 µm for doxorubicin and T-DM1, respectively) after the application of FUS compared with control (non-FUS). Integration of experimental data with physiologically based pharmacokinetic (PBPK) modeling of drug transport reveals that FUS in combination with microbubbles alleviates vascular barriers and enhances interstitial convective transport via an increase in hydraulic conductivity. Experimental data demonstrate that FUS in combination with microbubbles enhances significantly the endothelial cell uptake of the small chemotherapeutic agent. Quantification with PBPK modeling reveals an increase in transmembrane transport by more than two orders of magnitude. PBPK modeling indicates a selective increase in transvascular transport of doxorubicin through small vessel wall pores with a narrow range of sizes (diameter, 10-50 nm). Our work provides a quantitative framework for the optimization of FUS-drug combinations to maximize intratumoral drug delivery and facilitate the development of strategies to treat brain metastases.

Orthodontic emergencies and mental state of Chinese orthodontic patients during the COVID-19 pandemic.

BACKGROUND: The ongoing COVID-19 pandemic postponed routine follow-up visits of many orthodontic patients, which compromised their treatment process and mental states. This study was aimed to assess orthodontic emergency occurrence and psychological states of Chinese orthodontic patients during this pandemic. METHODS: Orthodontic patients in China were invited to answer an anonymous online questionnaire from February 20, 2020 to March 5, 2020, when routine dental care was suspended in China. The questionnaire included self-assessment of oral hygiene and compliance, orthodontic emergencies, perceptions and feelings about COVID-19 and anxiety self-rating scale, etc. Collected data was statistically analyzed with Chi-square, independent t test and univariable generalized estimating equations regression analysis. RESULTS: A total of 1078 respondents (292 male; 786 female) from 30 provinces of China were included in this study. About one-third (33.67%) of patients reported that they encountered orthodontic problems during the pandemic. Patients with clear aligners reported fewer orthodontic problems than those with fixed appliances or removable appliances. Female patients, elder patients and patients who encountered orthodontic emergencies were more anxious than other patients. CONCLUSIONS: The compliance and occurrence of orthodontic emergencies differed in patients with different orthodontic appliances. Patients with orthodontic emergencies exhibited higher anxiety states.

Calhex231 ameliorates myocardial fibrosis post myocardial infarction in rats through the autophagy-NLRP3 inflammasome pathway in macrophages.

The calcium-sensing receptor (CaSR) is involved in the pathophysiology of many cardiovascular diseases, including myocardial infarction (MI) and hypertension. The role of Calhex231, a specific inhibitor of CaSR, in myocardial fibrosis following MI is still unclear. Using Wistar rats, we investigated whether Calhex231 ameliorates myocardial fibrosis through the autophagy-NLRP3 inflammasome pathway in macrophages post myocardial infarction (MI). The rats were randomly divided into sham, MI and MI + Calhex231 groups. Compared with the sham rats, the MI rats consistently developed severe cardiac function, myocardial fibrosis and infiltration of inflammatory cells including macrophages. Moreover, inflammatory pathway including activation of NLRP3 inflammasome, IL-1ß and autophagy was significantly up-regulated in myocardial tissue, infiltrated cardiac macrophages and peritoneal macrophages of the MI rats. These impacts were reversed by Calhex231. In vitro, studies revealed that calindol and rapamycin exacerbated MI-induced autophagy and NLRP3 inflammasome activation in peritoneal macrophages. Calhex231 and 3-Methyladenine (a specific inhibitor of autophagy) attenuated both autophagy and NLRP3 inflammasome activation; however, the caspase-1 inhibitor Z-YVAD-FMK did not. Our study indicated that Calhex231 improved cardiac function and ameliorated myocardial fibrosis post MI, likely via the inhibition of autophagy-mediated NLRP3 inflammasome activation; this provides a new therapeutic target for ventricular remodelling-related cardiovascular diseases.

A Photowelding Strategy for Conductivity Restoration in Flexible Circuits.

Light-driven micropumps, which are based on electro-osmosis with the electric field generated by photocatalytic reactions, are among most attractive research topics in chemical micromotors. Until now, research in this field has mainly been focused on the directional motion or collective behavior of microparticles, which lack practical applications. In this study, we have developed a photowelding strategy for repeated photoinduced conductivity recovery of cracked flexible circuits. We immersed the circuit in a suspension of conductive healing particles and applied photoillumination to the crack; photocatalysis of a predeposited pentacene (PEN) layer triggered electro-osmotic effects to gather conductive particles at the crack, thus leading to conductivity recovery of the circuit. This photowelding strategy is a novel application of light-driven micropumps and photocatalysis for conductivity restoration.

The role of nervous system in adaptive response of bone to mechanical loading.

Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co-ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene-related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.

Chemical characterization and antitumor activities of polysaccharide extracted from Ganoderma lucidum.

Ganoderma lucidum polysaccharide (GLP) is a biologically active substance reported to possess anti-tumor ability. Nonetheless, the mechanisms of GLP-stimulated apoptosis are still unclear. This study aims to determine the inhibitory and apoptosis-inducing effects of GLP on HCT-116 cells. We found that GLP reduced cell viability on HCT-116 cells in a time- and dose-dependent manner, which in turn, induced cell apoptosis. The observed apoptosis was characterized by morphological changes, DNA fragmentation, mitochondrial membrane potential decrease, S phase population increase, and caspase-3 and -9 activation. Furthermore, inhibition of c-Jun N-terminal kinase (JNK) by SP600125 led to a dramatic decrease of the GLP-induced apoptosis. Western blot analysis unveiled that GLP up-regulated the expression of Bax/Bcl-2, caspase-3 and poly (ADP-ribose) polymerase (PARP). These results demonstrate that apoptosis stimulated by GLP in human colorectal cancer cells is associated with activation of mitochondrial and mitogen-activated protein kinase (MAPK) pathways.

A review on co-metabolic degradation of organic micropollutants during anaerobic digestion: Linkages between functional groups and digestion stages.

The emerging presence of organic micropollutants (OMPs) in water bodies produced by human activities is a source of growing concern due to their environmental and health issues. Biodegradation is a widely employed treatment method for OMPs in wastewater owing to its high efficiency and low operational cost. Compared to aerobic degradation, anaerobic degradation has numerous advantages, including energy efficiency and superior performance for certain recalcitrant compounds. Nonetheless, the low influent concentrations of OMPs in wastewater treatment plants (WWTPs) and their toxicity make it difficult to support the growth of microorganisms. Therefore, co-metabolism is a promising mechanism for OMP biodegradation in which co-substrates are added as carbon and energy sources and stimulate increased metabolic activity. Functional microorganisms and enzymes exhibit significant variations at each stage of anaerobic digestion affecting the environment for the degradation of OMPs with different structural properties, as these factors substantially influence OMPs' biodegradability and transformation pathways. However, there is a paucity of literature reviews that explicate the correlations between OMPs' chemical structure and specific metabolic conditions. This study provides a comprehensive review of the co-metabolic processes which are favored by each stage of anaerobic digestion and attempts to link various functional groups to their favorable degradation pathways. Furthermore, potential co-metabolic processes and strategies that can enhance co-digestion are also identified, providing directions for future research.