Macrophages in guided bone regeneration: potential roles and future directions.

Guided bone regeneration (GBR) is one of the most widely used and thoroughly documented alveolar bone augmentation surgeries. However, implanting GBR membranes inevitably triggers an immune response, which can lead to inflammation and failure of bone augmentation. It has been shown that GBR membranes may significantly improve in vivo outcomes as potent immunomodulators, rather than solely serving as traditional barriers. Macrophages play crucial roles in immune responses and participate in the entire process of bone injury repair. The significant diversity and high plasticity of macrophages complicate our understanding of the immunomodulatory mechanisms underlying GBR. This review provides a comprehensive summary of recent findings on the potential role of macrophages in GBR for bone defects in situ. Specifically, macrophages can promote osteogenesis or fibrous tissue formation in bone defects and degradation or fibrous encapsulation of membranes. Moreover, GBR membranes can influence the recruitment and polarization of macrophages. Therefore, immunomodulating GBR membranes are primarily developed by improving macrophage recruitment and aggregation as well as regulating macrophage polarization. However, certain challenges remain to be addressed in the future. For example, developing more rational and sophisticated sequential delivery systems for macrophage activation reagents; addressing the interference of bone graft materials and dental implants; and understanding the correlations among membrane degradation, macrophage responses, and bone regeneration.

Macrophages in periapical lesions: Potential roles and future directions.

Periapical lesions are infectious diseases that occur in the apical region of teeth. They result in the destruction of alveolar bone and are usually accompanied by swelling, pain, and possible systemic impacts. A complex interaction between pathogens and the host immune system determines the development, progression, and outcome of periapical lesions. The lesions, if not treated promptly, may cause resorption of bone tissue, destruction of the periodontal ligament, and loss of the affected teeth, all of which can severely worsen the quality of life of patients, often at considerable economic cost to both patients and medical organizations. Macrophages are a group of heterogeneous cells that have many roles in the development of infections, destruction and reconstruction of bone tissues, and microbe-host interactions. However, the differential and comprehensive polarization of macrophages complicates the understanding of the regulatory mechanism of periapical lesion progression. This report provides a comprehensive review of recent advances in our knowledge of the potential role of macrophages in determining the turnover of human periapical lesions. For example, macrophage differentiation might indicate whether the lesions are stable or progressing while the extent of bacteria invasion could regulate the differentiation and function of macrophages involved in the periapical lesion. In addition, alternative strategies for the treatment of apical periodontitis are discussed.

Multiplex DNA Walking Machines for Lung Cancer-Associated miRNAs.

Biomimetic DNA walking machines have gained great success in scrutinizing the microscopic world and sensitive biosensing of disease biomarkers. Despite superb achievements, the research on DNA walking machines for simultaneous detection of multiple analytes is still rare, while the design and realization of multiplexing are considered as an important bottleneck. The multiplex detection of biomarkers can not only improve the specificity of bioassays but also avoid the squander of valuable biological specimens. Herein, we reported multiplex three-dimensional (3D) DNA walking machines based on high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS) for lung cancer-associated miRNA detection. In the presence of lung cancer-associated target miRNAs (miR-21, miR-141, and miR-125b), DNA walking machines were stimulated and operated to liberate a large number of lanthanide elements (Tb, Ho, and Tm), and then the signals were collected simultaneously by HR-ICPMS. The recovery test of target miRNAs in human serum and the simultaneous monitoring experiment of three miRNAs in human lung cancer cell line (A549) and normal cell line (HBE) specimens display satisfactory analysis capabilities for complex biological samples. Thanks to the vast potential of lanthanide tags and the modular design, the proposed bioassay might flexibly detect different miRNA combinations with corresponding sets of DNA walking machines to meet the requirements of various tasks.

Analysis of influencing factors and prognosis of early postoperative recurrence, secondary tumor and metastasis of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world and it accounts for more than 90% of oral cancers. In this study, we tried to estimate the risk of early postoperative recurrence, secondary tumor and metastasis of OSCC to predict the patient's prognosis according to its clinical condition to help increase their survival by screening high-risk patients. 153 patients with OSCC who were over 40 years of age were studied during 1985-2020. The influencing factors included gender, race, stage of tumor progression, treatment method, histological grade and tumor location, date of diagnosis and death, which were analyzed by the Markov multi-state model. Also, their saliva was sampled to determine the amount of Matrix Metalloproteinase13 (MMP13). Following-up of patients for 60 months showed that one year after the end of treatment, the probability of death was almost the same for patients with early postoperative recurrence or secondary tumor, but after 5 years, patients with early postoperative recurrence are at higher risk of death. Also, the MMP13 amount in the saliva of patients showed that high levels of MMP13 belonged to metastasis of OSCC than early postoperative recurrence and secondary tumor. Therefore, patients with more amount of MMP13 are more involved in metastasis than early postoperative recurrence and secondary tumor. Approximate knowledge of OSCC patients' next state and time according to their clinical condition can be one of the ways of timely diagnosis and treatment and thus reduce their mortality rate.

Lanthanide Nanoprobes for the Multiplex Evaluation of Breast Cancer Biomarkers.

Metal stable isotope tagging has demonstrated great and unique success in the multiplex and ratiometry-based accurate detection of biomolecules and single cells, while its sensitivity is regarded as an Achilles' heel. Although lanthanide nanoparticles remain the most promising tags for elemental mass spectrometry, there is no report on the lanthanide nanoparticle-based multiplex immunoassay of disease markers in clinical serum samples because of their tough synthesis and bioconjugation and a complex physiological sample matrix. Herein, to fill this gap, multiple lanthanide nanoparticle tags (NaEuF4, NaTbF4, and NaHoF4) were delicately designed and facilely synthesized with a one-pot solvothermal method for the multiplex evaluation of breast cancer biomarkers carcinoembryonic antigen (CEA), CA153, and CA125 in human serum samples. The proposed method exhibited wide linear ranges and low levels of the detection limit for all biomarkers. The test results were consistent with the routine electrochemiluminescence results in clinical serum samples, which proved the possibility of the early prognosis of breast cancer as well as improving the surgical outcome prediction.

Clinicopathological features and lymph node metastasis risk in early gastric cancer with WHO criteria in China: 304 cases analysis.

AIMS: The aim of this research was to identify the clinicopathological characteristics of early gastric cancer (EGC) based on the WHO criteria, and to analyze predictors for lymph node metastasis (LNM) in EGC in a Chinese study population. METHODS: We retrospectively collected data of 304 Chinese EGC patients, including 265 patients undergoing radical gastrectomy and 39 patients undergoing endoscopic resection. Histological features were accessed by three experienced pathologists. Univariate analysis and multivariate analysis were used to identify the correlation between clinicopathological features and LNM. RESULTS: Among the 304 cases with EGC, the rate of well differentiated tubular adenocarcinoma was 11.2%, significantly lower than that of Japanese and South Korean, which was 24.8% and 19.9% respectively (p<0.001 and p = 0.006), but similar to that of a Western result, which was 11.9% (p = 0.860). Among the 265 patients who underwent gastrectomy, 18.5% of the patients had LNM. Univariate analysis showed that macroscopic type, differentiation degree, invasion depth, infiltration pattern (INF), lymphovascular invasion and ulceration were related to LNM. Multivariate analysis revealed that lymphovascular invasion (p < 0.001, OR = 6.549), ulceration (p = 0.035, OR = 2.527) and INF c (p = 0.042, OR = 3.424) were the independent risk factors of LNM in EGC. CONCLUSIONS: The pathological diagnosis standard of well differentiated tubular adenocarcinoma in China significantly differs from that in Japan and South Korea, but is similar to western countries. LNM is more likely to occur in EGCs with lymphovascular invasion, ulceration and INF c.

Multifunctional Reduced Graphene Oxide-Based Nanoplatform for Synergistic Targeted Chemo-Photothermal Therapy.

As for cancer treatments, synergistic therapy provides outstanding strategies to facilitate multiple anticancer pathways to induce improved therapeutic efficacy. Here, because of excellent physicochemical and biological properties, tea polyphenol-reduced and functionalized graphene oxide (TPG) was used to develop one single nanoplatform for synergistic targeted photo-chemotherapy. Specifically, a multifunctional nanoplatform with anti-PDL1-conjugated TPG (TPDL1) as a targeted therapy, loading the anticancer drug doxorubicin hydrochloride (DOX) on TPDL1 (TPD) as chemotherapy, and TPDL1 as a photothermal agent with near-infrared (NIR) irradiation as photothermal therapy (PTT) was constructed to reduce side effects and enhance the therapeutic efficacy. As expected, the nanoplatform showed NIR-enhanced, pH-responsive, and stable drug release behavior, targeting ability, and efficient photothermal conversion under NIR irradiation. Compared with pure DOX, TPD not only did protect normal cells from side effects but also efficiently enhanced the cytotoxicity in human tongue squamous cancer cells (CAL27) under NIR laser irradiation, which may be due to the synergistic effects between DOX-induced chemotherapy and TPDL1-elicited PTT. This study shows that the multifunctional reduced graphene oxide-based nanoplatform with combined targeted chemo-PTT has potential application values in cancer therapy.

Cataluminescence Coupled with Photoassisted Technology: A Highly Efficient Metal-Free Gas Sensor for Carbon Monoxide.

With the development of green chemistry, metal-free nanocatalysts have gradually substituted metal-based materials, causing widespread concern among researchers in many fields, especially in cataluminescence sensing, because of their long-term stability and environmental friendliness as well as low costs. Besides the catalysts, innovations of assistant technologies for cataluminescence are needed to enhance the oxidation reactivity of the gas molecules or catalytic efficiency of sensing materials. Although, there are some groups enhancing the cataluminescence reaction via various assistant technologies, the development of assistant technologies in cataluminescence sensors is still in its infancy; the design, effect mechanism, and application are still stimulating challenges. Herein, with photodynamic assistant, fluorinated nanoscale hexagonal boron nitride is first employed as a metal-free catalyst to establish a novel cataluminescence method for detecting CO gases, and the cataluminescence reaction mechanism of CO is also investigated in detail. Under the best conditions, the detection limit (3σ) of the CO concentration is 0.005 µg mL-1, which has been largely improved in cataluminescence methods. The realization of detection of CO from theory to practice through the method of cataluminescence is beneficial for the practical application of metal-free catalysts to detect CO rather than staying at the possibility to detect CO by means of theoretical calculation only.

High-throughput LC-MS/MS method with 96-well plate precipitation for the determination of arotinolol and amlodipine in a small volume of rat plasma: Application to a pharmacokinetic interaction study.

A rapid, sensitive, and selective liquid chromatography with tandem mass spectrometry method was developed and fully validated for the simultaneous quantification of arotinolol and amlodipine in rat plasma. Two internal standards were introduced with metoprolol as the internal standard of arotinolol and (S)-amlodipine-d4 as the internal standard of amlodipine. The analytes were isolated from 50.0 µL plasma samples by a simple protein precipitation using acetonitrile. The chromatographic separation was achieved in 5 min on a C18 column. The mobile phase consisted of phase A 5% methanol and phase B 95% methanol (both containing 0.5% formic acid and 5 mM ammonium acetate) and was delivered in gradient elution at 0.300 mL/min. Quantification was performed in multiple reaction monitoring mode with the transition m/z 372.1 â†’ 316.1 for arotinolol, m/z 268.2 â†’ 116.2 for metoprolol, m/z 409.1 â†’ 238.1 for amlodipine and m/z 413.1 â†’ 238.1 for (S)-amlodipine-d4. Linearity was obtained over the range of 0.200-40.0 ng/mL for arotinolol (r2  = 0.9988) and 0.500-100 ng/mL for amlodipine (r2  = 0.9985) in rat plasma. The validated data have met the acceptance criteria in FDA guideline. This method was successfully applied to a pharmacokinetic interaction study in rats, and the results indicated that there was no significant drug-drug interaction between arotinolol and amlodipine.

Highly sensitive cataluminescence gas sensors for 2-butanone based on g-C3N4 sheets decorated with CuO nanoparticles.

A simple and facile ultrasound-assisted and calcining synthesis route was used to synthesize g-C3N4 sheets decorated with CuO nanoparticles (CuO/g-C3N4). On the basis of the XRD, XPS as well as TEM analysis, CuO nanoparticles which have high density and uniformity were evenly dispersed on g-C3N4 sheets to form a heterogeneous composite. The CuO/g-C3N4 composite was fabricated to be a gas sensor for 2-butanone, a common volatile organic compound, based on the interesting cataluminescence (CTL) phenomenon of 2-butanone originating from its catalyzing oxidation on the surface of CuO/g-C3N4 composite. The analytical characteristics of the CTL sensor based on CuO/g-C3N4 composite sensing material for 2-butanone were systematically investigated under the optimal experimental conditions. It demonstrated a fast response and recovery time about less than 2 and 40 s, respectively. The linear range of the 2-butanone gas sensor was 16.11-161.08 µg mL-1 (r = 0.998) and the limit of detection was 11.06 µg mL-1 (S/N = 3).

MiR-27a-3p promotes esophageal cancer cell proliferation via F-box and WD repeat domain-containing 7 (FBXW7) suppression.

Emerging evidence has suggested that dysregulation of microRNA-27a-3p (miR-27a-3p) may contribute to tumor development and progression in various types of cancers. However, its role in esophageal cancer is still unknown. In the present study, miR-27a-3p was significantly increased in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. In esophageal cancer Eca109 cells, ectopic overexpression of miR-27a-3p promoted cell proliferation, meanwhile, cell proliferation was reduced by miR-27a-3p inhibition. Further studies showed that down-regulated miR-27a-3p expression could induced cell cycle arrest at the G1/S transition. In exploring mechanisms underlying the promotive role, our results revealed that miR-27a-3p markedly inhibited the expression of F-box and WD repeat domain-containing 7 (FBXW7). FBXW7, a tumor suppressor, exhibited significantly inhibitory effect on Eca109 cell proliferation. Thus our observations suggested that miR-27a-3p functioned as a tumor suppressor by targeting FBXW7. These findings indicated that miR-27a-3p could be considered as a potential therapeutic strategy for ESCC therapy.

A metal (Co)-organic framework-based chemiluminescence system for selective detection of L-cysteine.

A metal (Co)-Organic Framework (Co-MOF) was first found to catalyze the chemiluminescence (CL) of luminol. On the basis of X-ray photoelectron spectroscopy, powder X-ray diffraction, CL spectral, UV-visible absorption spectral, and electron spin resonance (ESR) spectral studies, as well as the research of the influence of various free radical scavengers, a possible CL mechanism was proposed. The enhanced CL might be attributed to the formation of a peroxide analogous complex between the oxygen-related radicals and the active metal site of the Co-MOF material. The established Co-MOF-luminol CL system was successfully applied to determine L-cysteine (CySH), based on the selective and sensitive enhancing effect of CySH on this CL system. Under the optimized conditions, CySH was selectively detected in the range 0.1-10 µM with a detection limit of 18 nM. This novel CL system obviously gives impetus to the new research field of metal-organic frameworks (MOFs) in chemiluminescence.

Prevalence of atrial fibrillation and its risk factors in rural China: a cross-sectional study.

OBJECTIVES: To evaluate the prevalence of atrial fibrillation (AF) in physical laborers in rural China and identify contributing risk factors. METHODS: A cross-sectional study of 11,956 permanent residents of Liaoning Province in rural China≥35y of age (primarily physical laborers) was conducted between January and August 2013 (response rate 85.3%). All participants completed a questionnaire and underwent a physical exam, echocardiography and electrocardiography. Blood samples were drawn for laboratory analyses, and AF was diagnosed on the basis of history and electrocardiograph findings. Risk factors for AF were evaluated with a stepwise logistic regression analysis. RESULTS: The prevalence of AF was 1.2% overall, but rose steeply with age (0.1% in those 35-44y of age, and 4.6% in those≥75y); there was no significant gender difference at any age. Independent risk factors for AF were age (odds ratio [OR] 1.89; P<0.001), diabetes (OR 2.07; P=0.001), history of myocardial infarction (OR 5.91; P<0.001), low left ventricular ejection fraction (OR 1.85; P=0.005), and low physical activity (OR 1.72; P=0.003), whereas obesity, hypertension, cholesterol and triglyceride levels, current smoking and drinking, left ventricular hypertrophy, and family history of AF were not significant contributors. CONCLUSIONS: Although the prevalence of AF in physical labors in rural China is low, age, diabetes, history of myocardial infarction, low left ventricular ejection fraction, and low physical activity are independent risk factors.

Turn-on persistent luminescence probe based on graphitic carbon nitride for imaging detection of biothiols in biological fluids.

Herein, we present a novel strategy based on a "turn-on" persistent luminescence imaging chemical system of graphitic carbon nitride for detecting biothiols in biological fluids. Graphitic carbon nitride (g-C3N4) as persistent luminescence probe is fabricated via a new procedure based on pyrolysis of guanidine hydrochloride under ambient atmospheric conditions. The prepared g-C3N4 nanosheets give intensively long-persistent luminescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The original persistent luminescence of g-C3N4 turns off due to the adsorption of silver ion (Ag(+)) onto g-C3N4 materials with an electron transfer process. The presence of biothiols induces the onset of persistent luminescence emission by interrupting the quenching interaction, thereby turning on the imaging probe. The approach exhibits high specificity and high sensitivity to biothiols with low detection limit for cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) with 6.4, 8.1, and 9.6 nM, respectively. It is also successfully applied for imaging detection of biothiols in human urine, plasma, and cell lysates, demonstrating its great value of practical application in biological systems.

Microwave-assisted green synthesis of ultrasmall fluorescent water-soluble silver nanoclusters and its application in chiral recognition of amino acids.

In this article, we established a fluorescent chiral recognition and detection method for cysteine based on the L-glutathione (L-GSH)-stabilized Ag nanoclusters (AgNCs) with high selectivity and sensitivity. A fast and green microwave (MW)-assisted strategy has been employed for synthesizing water-soluble fluorescent L-GSH-AgNCs. The reaction time was shortened from hours to several minutes. The synthetic process utilized L-glutathione as a stabilizing agent and a reducing agent without any other toxic reducing agent, such as NaBH4 or N2H4. The method is environmental friendly. Due to the different responses to AgNCs from chiral cysteine, we found d-cysteine hardly affects the fluorescence intensity of the AgNCs, whereas L-cysteine distinctly weakened its fluorescence intensity. This experiment indicated that fluorescence quenching efficiency of AgNCs was proportional to the concentration of L-cysteine in the range from 0.025 to 50 µmol L(-1).

[Mucinous tubular and spindle cell carcinoma of kidney: a clinicopathological study].

OBJECTIVE: To investigate the clinicopathological features, histogenesis and prognosis of mucinous tubular and spindle cell carcinoma (MTSCC). METHODS: Five MTSCCs were studied with histochemical, immunohistochemical staining, electron microscopy, and review of the related literatures. RESULTS: Four cases of MTSCC were females and one was male. Three patients presented with flank discomfort and two were incidentally found with health examination. In gross examination, the tumors were circumscribed. The cut surface was solid, gray-white, yellow or red. Necrosis was present in one case of high-grade MTSCC. Microscopically, low-grade MTSCC was mainly consisted of tubular, spindle cell and mucinous stroma with relatively bland morphology, and mitoses were rare. While in the high-grade area of one case, the cells were spindle or polymorphic with severe atypia and high mitotic activity, without mucinous stroma and tubular structure. Mucin was positive for Alcian blue. The neoplastic cells were positive for vimentin (5/5), CKpan (5/5), CK7 (5/5), CK19 (5/5), 34betaE12 (1/5), EMA (5/5), E-cadherin (3/5), CD10 (1/5), P504S (5/5), and CAM5.2 (5/5). The Ki-67 index was low (< or = 5%) in the low-grade component, while it was high (15%) in the high-grade component. Ultrastructural study showed short microvilli along glandular lumens. The nuclear membrane was focally invaginated. Four cases were followed up for 3 to 52 months, and recurrence and metastasis were not found. CONCLUSIONS: MTSCC occurs predominantly in females and it is a rare kidney neoplasm. Most of MTSCCs are low-grade and the prognosis is relatively good. However, the patients of high-grade MTSCC should be closely followed up.

[Experimental study on the reconstruction of bone defects in vivo and the osteoinduction with degradation products of alpha-tricalcium phosphate cements in vitro].

OBJECTIVE: This study was aimed to clarify the characteristics of alpha-tricalcium phosphate cements in reconstructing bone defects and the action of degradation products of cements in vitro. METHODS: The defect (diameter 1.5 cm) was created in the calvaria of rabbit. Alpha-tricalcium phosphate cements were planted in the treatment groups. All groups were observed by histological examination and roentgenography. Bone marrow stromal cells (BMSc) were cultured in the degradation products of cements in vitro, and were observed by means of cytology and ALP. RESULTS: Degradation of artificial bone, new bone formation, and osteogenesis between artificial bone particles were observed at 12 weeks after implantation. Osteoinduction was observed in vitro. CONCLUSION: Alpha-tricalcium phosphate cements have good biocompatibility, osteoinductivity and degradability, and are ideal bone substitute material for reconstruction.