Structure-decoupled functional connectome-based brain age prediction provides higher association to cognition.

Brain age prediction as well as the prediction difference has been well examined to be a potential biomarker for brain disease or abnormal aging process. However, less knowledge was reported for the cognitive association within normal population. In this study, we proposed a novel approach to brain age prediction by structure-decoupled functional connectome. The original functional connectome was decomposed and decoupled into a structure-decoupled functional connectome using structural connectome harmonics. Our method was applied to a large dataset of normal aging individuals and achieved a high correlation between predicted and chronological age (r = 0.77). Both the original FC and structure-decoupled FC could be well-trained in a brain age prediction model. Significant remarkable relationships between the brain age prediction difference (predicted age minus chronological age) and cognitive scores were discovered. However, the brain age-predicted difference driven by structure-decoupled FC showed a stronger correction to the two cognitive scores (MMSE: r = -0.27, P -value = 0.002; MoCA: r = -0.32, P -value = 0.0003). Our findings suggest that our structure-decoupled functional connectivity approach could provide a more individual-specific functional network, leading to improved brain age prediction performance and a better understanding of cognitive decline in aging.

Cellular uptake, intracellular behavior, and acute/sub-acute cytotoxicity of a PEG-modified quantum dot with promising in-vivo biomedical applications.

Quantum Dots (QDs) modified with branched Polyethylene Glycol-amine (6- or 8-arm PEG-amine) coupled with methoxy PEG (mPEG) hold great promise for in vivo biomedical applications due to a long half-life in blood and negligible toxicity. However, the potential risks regarding their concomitant prolonged co-incubation with cardiovascular and blood cells remains inconclusive. In the present study, the feasible, effective and convenient proliferating-restricted cell line models representing the circulatory system were established to investigate the cellular internalization followed by intracellular outcomes and resulting acute/sub-acute cytotoxicity of the 6-arm PEG-amine/mPEG QDs. We found a dose-, time- and cell type-dependent cellular uptake of the 6-arm PEG-amine/mPEG QDs, which was ten-fold lower compared to the traditional linear PEG-modified counterpart. The QDs entered cells via multiple endocytic pathways and were mostly preserved in Golgi apparatus for at least one week instead of degradation in lysosomes, resulting in a minimal acute cytotoxicity, which is much lower than other types of PEG-modified QDs previously reported. However, a sub-acute cytotoxicity of QDs were observed several days post exposure using the concentrations eliciting no-significant acute cytotoxic effects, which was associated with elevated ROS generation caused by QDs remained inside cells. Finally, a non-cytotoxic concentration of the QDs was identified at the sub-acute cytotoxic level. Our study provided important information for clinical translation of branched PEG-amine/mPEG QDs by elucidating the QDs-cell interactions and toxicity mechanism using the proliferation-restricted cell models representing circulatory system. What's more, we emphasized the indispensability of sub-acute cytotoxic effects in the whole biosafety evaluation process of nanomaterials like QDs.

Pseudomonas composti isolate from oyster digestive tissue specifically binds with norovirus GII.6 via Psl extracellular polysaccharide.

Oysters are recognized as important vectors for human norovirus transmission in the environment. Whether norovirus binds to bacteria in oyster digestive tissues (ODTs) remains unknown. To shed light on this concern, ODT-54 and ODT-32, positive for histo-blood group antigen (HBGA) -like substances, were isolated from ODTs and identified as Pseudomonas composti and Enterobacter cloacae, respectively. The binding of noroviruses (GII.4 and GII.6 P domains) to bacterial cells (ODT-32 and ODT-54; in situ assay) as well as extracted extracellular polysaccharides (EPSs; in vitro assay) was analyzed by flow cytometry, confocal laser scanning microscopy, ELISA, and gene knock-out mutants. ODT-32 bound to neither GII.4 nor GII.6 P domains, while ODT-54 specifically binds with GII.6 P domain through Psl, an exopolysaccharide encoded by the polysaccharide synthesis locus (psl), identified based on gene annotation, gene transcription, Psl specific staining, and ELISAs. These findings attest that ODT bacteria specifically bind with certain norovirus genotypes in a strain-dependent manner, contributing to a better understanding of the transmission and enrichment of noroviruses in the environment.

Effective suppression of triple negative breast cancer by paclitaxel nanoparticles conjugated with transmembrane TNF-α monoclonal antibody.

Transmembrane TNF-α (tmTNF), a transmembrane form of TNF-α, was reported overexpressed in approximately 84% of triple-negative breast cancer (TNBC) patients and has emerged as a valid candidate biomarker for targeting TNBC. Paclitaxel is a first-line chemotherapeutic agent for the treatment of triple-negative breast cancer, but suffers from low water solubility, resulting in its low bioavailability. To achieve site-specific delivery of the anticancer chemotherapeutic drug (paclitaxel) on TNBC, we developed tmTNF-α monoclonal antibody (mAb)-conjugated paclitaxel (PTX) nanoparticles (NPs) (tmTNF-α mAb-PTX NPs) as potential nanocarriers. This targeted delivery-therapy nanocarriers was conducted by using an emulsification-evaporation method. tmTNF-α mAb-PTX NPs displayed favorable physicochemical properties. Compared with the control groups, tumor growth in human MDA-MB-231 xenograft mice was suppressed significantly by tmTNF-α mAb-PTX NPs. TmTNF-α mAb-PTX NPs exerts anti-tumor effects via promoting apoptosis and regulating mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) / protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) cascade, as well as AMP-activated protein kinase (AMPK) and nuclear factor Kappa-B (NF-κB) pathways. Moreover, tmTNF-α mAb-PTX NPs can inhibit the process of epithelial-mesenchymal transition (EMT) in TNBC to suppress tumor progression and metastasis. Together, the novel tmTNF-α mAb-PTX NPs based targeted drug delivery system is a potentially highly effective approach for treating TNBC.

Efficacy of traditional Chinese medicine injections for treating idiopathic pulmonary fibrosis: A systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), acutely or slowly progressing into irreversible pulmonary disease, causes severe damage to patients' lung functions, as well as death. In China, Chinese medicine injections (CMIs) have been generally combined with Western medicine (WM) to treat IPF, which are safe and effective. This study aimed to systematically compare the efficacy of 14 CMIs combined with WM in the treatment of IPF based on a systematic review and network meta-analysis (NMA). MATERIAL AND METHODS: PubMed, Web of Science, Embase, Cochrane Library, MEDLINE, and Chinese databases, including the China National Knowledge Infrastructure, Wanfang Database, Scientific Journal Database, and China Biology Medicine Database were searched from inception to October 31, 2021. The inclusion criterion was randomized controlled trials (RCTs) on CMIs with WM for treating IPF. Reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.4 software and Stata software (version 16.0) were used for the data analysis. NMA were carried out for calculating the odd ratios (ORs) with 95% confidence intervals (CI), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best. RESULTS: A total of 63 eligible RCTs involving 14 CMIs were included in this NMA. More CMIs can significantly improve the clinical effectiveness rate (CER); Shuxuening injection (SXN)+WM (OR 8.91, 95% CI 3.81-20.83), Shuxuetong injection (SXT)+WM (OR 7.36, 95% CI 3.30-16.00), Shenxiong injection (SX)+WM (OR 5.42, 95% CI 2.90-10.13), Danhong injection (DH)+WM (OR 4.06, 95% CI 2.62-6.29), and Huangqi injection (HQ)+WM (OR 3.47, 95% CI 1.55-7.77) were the top five treatment strategies. Furthermore, DH +WM ranked relatively high in the SUCRA value of the nine outcome indicators, oxygen partial pressure (PaO2) (OR -13.39; 95% CI -14.90,-11.89; SUCRA 83.7%), carbon dioxide partial pressure (PaCO2) (OR -4.77; 95% CI -5.55,-3.99; SUCRA 83.3), orced vital capacity (FVC) (OR -1.42; 95% CI -2.47,-0.36; SUCRA 73.5%), total lung capacity (TLC) (OR 0.93; 95% CI 0.51,1.36; SUCRA 89.0%), forced expiratory volume 1/ forced vital capacity (FEV1/FVC%) (OR -10.30; 95% CI -12.98,-7.62; SUCRA 72.7%), type III collagen (IIIC) (OR 13.08; 95% CI 5.11,21.05; SUCRA 54.9%), and transforming growth factor (TGF) (OR -4.22; 95% CI -6.06,-2.37; SUCRA 85.7%) respectively, which seems to indicate that DH+WM had the highest likelihood of being the best treatment. CONCLUSIONS: This review specified several CMIs combined with WM in the treatment of IPF in China. In contrast to glucocorticoids or antioxidants, CMIs combined with WM delayed the decline in lung function, maintained oxygenation and quality of life in patients with IPF. The combined use of DH, SXN, SX, and safflower yellow sodium chloride injection (HHS) with WM exerted a more positive effect in treating IPF than WM alone. However, there were limitations to the conclusions of this study due to quality control differences in the included trials.

Multifunctional Gelatin-Nanoparticle-Modified Chip for Enhanced Capture and Non-Destructive Release of Circulating Tumor Cells.

Circulating tumor cells (CTCs) in cancer patients' peripheral blood have been demonstrated to be a significant biomarker for metastasis detection, disease prognosis, and therapy response. Due to their extremely low concentrations, efficient enrichment and non-destructive release are needed. Herein, an FTO chip modified with multifunctional gelatin nanoparticles (GNPs) was designed for the specific capture and non-destructive release of CTCs. These nanoparticles share a similar dimension with the microvilli and pseudopodium of the cellular surface; thus, they can enhance adhesion to CTCs, and then GNPs can be degraded by the enzyme matrix metalloproteinase (MMP-9), gently releasing the captured cells. In addition, the transparency of the chip makes it possible for fluorescence immunoassay identification in situ under a microscope. Our chip attained a high capture efficiency of 89.27%, a release efficiency of 91.98%, and an excellent cellular viability of 96.91% when the concentration of MMP-9 was 0.2 mg/mL. Moreover, we successfully identified CTCs from cancer patients' blood samples. This simple-to-operate, low-cost chip exhibits great potential for clinical application.

Construction and validation of a transcription factors-based prognostic signature for ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is one of the most common and lethal malignant tumors worldwide and the prognosis of OC remains unsatisfactory. Transcription factors (TFs) are demonstrated to be associated with the clinical outcome of many types of cancers, yet their roles in the prognostic prediction and gene regulatory network in patients with OC need to be further investigated. METHODS: TFs from GEO datasets were collected and analyzed. Differential expression analysis, WGCNA and Cox-LASSO regression model were used to identify the hub-TFs and a prognostic signature based on these TFs was constructed and validated. Moreover, tumor-infiltrating immune cells were analyzed, and a nomogram containing age, histology, FIGO_stage and TFs-based signature were established. Potential biological functions, pathways and the gene regulatory network of TFs in signature was also explored. RESULTS: In this study, 6 TFs significantly associated with the prognosis of OC were identified. These TFs were used to build up a TFs-based signature for predicting the survival of patients with OC. Patients with OC in training and testing datasets were divided into high-risk and low-risk groups, according to the median value of risk scores determined by the signature. The two groups were further used to validate the performance of the signature, and the results showed the TFs-based signature had effective prediction ability. Immune infiltrating analysis was conducted and abundance of B cells naïve, T cells CD4 memory resting, Macrophages M2 and Mast cells activated were significantly higher in high-risk group. A nomogram based on the signature was established and illustrated good predictive efficiencies for 1, 2, and 3-year overall survival. Furthermore, the construction of the TFs-target gene regulatory network revealed the potential mechanisms of TFs in OC. CONCLUSIONS: To our best knowledge, it is for the first time to develop a prognostic signature based on TFs in OC. The TFs-based signature is proven to be effective in predicting the survival of patients with OC. Our study may facilitate the clinical decision-making for patients with OC and help to elucidate the underlying mechanism of TFs in OC.

Clinical features of 162 fatal cases of COVID-19: a multi-center retrospective study.

Background: The coronavirus disease 2019 (COVID-19) has affected approximately 2 million individuals worldwide; however, data regarding fatal cases have been limited. Objective: To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30, 2019 and March 12, 2020. Methods: The demographic data, signs and symptoms, clinical course, comorbidities, laboratory findings, computed tomographic (CT) scans, treatments, and complications of the patients with fatal cases were retrieved from electronic medical records. Results: The median patient age was 69.5 (interquartile range: 63.0-77.25) years, and 80% of the patients were over 61 years. A total of 112 (69.1%) patients were men. Hypertension (45.1%) was the most common comorbidity, while 59 (36.4%) patients had no comorbidity. At admission, 131 (81.9%) patients had severe or critical COVID-19, whereas 39 (18.1%) patients with hypertension or chronic lung disease had moderate COVID-19. In total, 126 (77.8%) patients received antiviral treatment, while 132(81.5%) patients received glucocorticoid treatment. A total of 116 (71.6%) patients were admitted to the intensive care unit (ICU), and 137 (85.1%) patients received mechanical ventilation. Most patients received mechanical ventilation before ICU admission. Approximately 93.2% of the patients developed respiratory failure or acute respiratory distress syndrome. There were no significant differences in the inhospital survival time among the hospitals (P=0.14). Conclusion: Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes. The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.

Multi-step purification of electrolytic manganese residue leachate using hydroxide sedimentation, struvite precipitation, chlorination and coagulation: Advanced removal of manganese, ammonium, and phosphate.

Water pollution caused by the release of manganese (Mn2+) and ammonia nitrogen (NH4+-N) from electrolytic manganese residue (EMR) generated from industrial activities poses a serious threat to ecosystems and human health. In this study, an integrated process consisting sequentially of hydroxide sedimentation, struvite precipitation, breakpoint chlorination, and ferric chloride coagulation was optimized to remove Mn2+ and NH4+-N from EMR leachate, and to address the issue of residual orthophosphate caused by struvite precipitation. The precipitates were characterized using X-ray diffraction, scanning electron microscopy, and thermogravimetric analyses. Results show that Mn2+ ions and the resulting chemical oxygen demand (COD) were mainly removed using hydroxide precipitation at a sedimentation pH of 10.2, with poor-crystalline manganese hydroxide as the main precipitate. NH4+-N was primarily removed and recovered using struvite precipitation with well crystalline struvite as the main product, and then further eliminated using breakpoint chlorination. The residual orthophosphate introduced by struvite precipitation is successfully removed with ferric coagulation, and the effluent pH (7.5) is also lowered to discharge limits by means of hydrolysis of ferric coagulant. The concentration of COD, Mn2+, NH4+-N, and orthophosphate concentrations in the final effluent were 30.52 ± 9.38, 0.026 ± 0.013, 0.87 ± 0.01, and 0.06 ± 0.002 mg/L, respectively, meeting all local discharge standards. This combined process has robust pollutant removal efficiency, high resource recovery potential and few environmental constraints; thus, it is recommended as a potential solution for the treatment of Mn2+- and NH4+-N-rich acid mine drainage.

Mechanically Induced Switching between Two Discrete Conductance States: A Potential Single-Molecule Variable Resistor.

The fabrication of solid-state single-molecule switches with high on-off conductance ratios has been proposed to advance conventional technology in areas such as molecular electronics. Herein, we employed the scanning tunneling microscope break junction (STM-BJ) technique to modulate conductance in single-molecule junctions using mechanically induced stretching. Compound 1a possesses two dihydrobenzothiophene (DHBT) anchoring groups at the opposite ends linked with rigid alkyne side arms to form a gold-molecule-gold junction, while 1b contains 4-pyridine-anchoring groups. The incorporation of ferrocene into the backbone of each compound allows rotational freedom to the cyclopentadienyl (Cp) rings to give two distinct conductance states (high and low) for each. Various control experiments and suspended junction compression/retraction measurements indicate that these high- and low-conductance plateaus are the results of conformational changes within the junctions (extended and folded states) brought about by mechanically induced stretching. A high-low switching factor of 42 was achieved for 1a, whereas an exceptional conductance ratio in excess of 2 orders of magnitude (205) was observed for 1b. To the best of our knowledge, this is the highest experimental on-off conductance switching ratio for a single-molecule junction exploiting the mechanically induced STM-BJ method. Computational studies indicated that the two disparate conductance states observed for 1a and 1b result from mechanically induced conformational changes due to an interplay between conductance and the dihedral angles associated with the electrode-molecule interfaces. Our study reveals the structure-function relationship that determines conductance in such flexible and dynamic systems and promotes the development of a single-molecule variable resistor with high on-off switching factors.

The effect of early systematic rehabilitation nursing on the quality of life and limb function in elderly patients with stroke sequelae.

OBJECTIVE: To study the effect of early systematic rehabilitation nursing on the quality of life and limb function in elderly patients with stroke sequelae. METHODS: This prospective study was conducted in 97 elderly patients with stroke sequelae. These patients were randomly allocated to the control group (n=49) and the experimental group (n=48). Patients in the control group received routine rehabilitation nursing, while those in the experimental group received early systematic rehabilitation nursing. Upper limb motor function (Fugl-Meyer assessment (FMA) score), upper limb sensory function (tactile threshold and two-point discrimination), physiological state (Hamilton anxiety (HAMA) scale and Hamilton depression (HAMD) scale score), ability of daily living (ADL) (the Barthel index score and ability of daily living score), and the quality of life (generic quality of life inventory-74 (GQOLI-74) score) before and 3 months after intervention were compared between the two groups. RESULTS: Compared with before intervention, FMA scores in the two groups after intervention were increased, while modified Ashworth scores were decreased (all P<0.05). The changes in the experimental group after intervention were more than those in the control group (both P<0.05). Tactile threshold and two-point discrimination in both groups after intervention were reduced when compared with before intervention (all P<0.05); tactile threshold and two-point discrimination in the experimental group after intervention group were smaller than those in the control group (both P<0.05). HAMA scale and HAMD scale scores in the two groups after intervention were lower than those before intervention (all P<0.05); HAMA scale and HAMD scale score in the experimental group after intervention were reduced when compared with the control group (both P<0.05). The Barthel index scores, ADL scores, and GQOLI-74 scores in both groups after intervention were increased when compared with before intervention (all P<0.05). The Barthel index score, ADL score, and GQOLI-74 score in the experimental group after intervention were higher than those in the control group (all P<0.05). CONCLUSION: For elderly patients with stroke sequelae, early systemic rehabilitation nursing is more beneficial for the improvement of upper limb motor and sensory function, alleviation of negative psychology, raise in ability of daily living, and increase of life quality. It is therefore worthy of clinical application.

Low-Cost and Scalable Platform with Multiplexed Microwell Array Biochip for Rapid Diagnosis of COVID-19.

Sensitive detection of SARS-CoV-2 is of great importance for inhibiting the current pandemic of COVID-19. Here, we report a simple yet efficient platform integrating a portable and low-cost custom-made detector and a novel microwell array biochip for rapid and accurate detection of SARS-CoV-2. The instrument exhibits expedited amplification speed that enables colorimetric read-out within 25 minutes. A polymeric chip with a laser-engraved microwell array was developed to process the reaction between the primers and the respiratory swab RNA extracts, based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP). To achieve clinically acceptable performance, we synthesized a group of six primers to identify the conserved regions of the ORF1ab gene of SARS-CoV-2. Clinical trials were conducted with 87 PCR-positive and 43 PCR-negative patient samples. The platform demonstrated both high sensitivity (95.40%) and high specificity (95.35%), showing potentials for rapid and user-friendly diagnosis of COVID-19 among many other infectious pathogens.

Characterization of cadmium biosorption by inactive biomass of two cadmium-tolerant endophytic bacteria Microbacterium sp. D2-2 and Bacillus sp. C9-3.

In this study, two cadmium-tolerant endophytic bacteria (Microbacterium sp. D2-2 and Bacillus sp. C9-3) were employed as biosorbents to remove Cd(II) from aqueous solutions. The influence of initial pH, initial Cd(II) concentration, adsorbent biomass, temperature and contact time on Cd(II) removal were investigated. Results showed that the Langmuir isotherms were found to best fit the equilibrium data, and the maximum biosorption capacities were found to be 222.22 and 163.93 mg/g at a solution pH of 5.0 for Microbacterium sp. D2-2 and Bacillus sp. C9-3, respectively. The biosorption kinetics followed well pseudo-second-order kinetics. Fourier transform infrared spectroscopic analysis suggested that the hydroxyl, carboxyl, carbonyl and amino groups on Microbacterium sp. D2-2 and Bacillus sp. C9-3 biomass were the main binding sites for Cd(II). The results presented in this study showed that Microbacterium sp. D2-2 and Bacillus sp. C9-3 are potential and promising adsorbents for the effective removal of Cd(II) from aqueous solutions.

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response.

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-ß levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-ß responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.

Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.

Prognostic Role of S100A8 in Human Solid Cancers: A Systematic Review and Validation.

BACKGROUND: S100A8 plays a key role in many cellular processes and is highly expressed in various solid cancers. However, the prognostic role of S100A8 has not been well defined. Therefore, we conducted a quantitative meta-analysis to investigate whether or not S100A8 could be used as a prognostic biomarker in solid tumors. METHODS: PubMed, Web of Science, Embase, and Cochrane library were searched to acquire relevant studies that evaluated the association between expression of S100A8 and prognosis of cancer patients. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were extracted to evaluate the association between S100A8 overexpression and Overall Survival (OS), Disease-Free Survival (DFS), Recurrence-Free Survival (RFS), and Progression-Free Survival (PFS). The expression of S100A8 was also validated by Flow cytometry, immunohistochemistry (IHC), and western blot. RESULTS: A total of 2,817 patients from 13 independent studies, ranging from 43 to 1,117 patients in size, were statistically analyzed. Our results indicated that a high level of S100A8 expression was significantly associated with poor OS, poor DFS, and poor PFS/RFS. In term of clinical pathological characteristics, a high expression level of S100A8 was significantly associated with differentiation grades, lymphatic metastasis, ER statue, and PR statue. The validation studies showed that the expression of S100A8 was at high levels in MDA-MB-231 (79.7%), MDA-MB-453 (89.2%), HTB-9 (70.2%), and T24 (53.3%) cells and it was higher in breast cancer tissue and bladder cancer tissue than their corresponding para-carcinoma tissue. CONCLUSIONS: S100A8 overexpression was significantly associated with poor clinical prognosis in cancer patients. S100A8 is potential a prognostic biomarker in breast cancer and bladder cancer. More well-designed studies with adequate prognostic data are needed to confirm the prognostic role of S100A8 revealed in this study.

Electrospun degradable Zn-Mn oxide hierarchical nanofibers for specific capture and efficient release of circulating tumor cells.

Constructing biological affinity devices is considered as an effective strategy for isolating circulating tumor cells (CTCs), and electrospun nanofibers (ESNFs) have recently received attention. However, the current research focuses on polymer fibers, and fabricating stimuli-responsive inorganic nanofibers for cancer diagnosis and analysis is still challenging. In this work, Zn-Mn oxide nanofibers (ZnMnNFs) are used to capture and purify cancer cells after modification with specific antibodies. Then, the hierarchical nanofibers are degraded by reductive weak acid to release the captured cells efficiently without residues. Fusion of Zn and Mn, two transition metals, enhances the surface activity of oxides so that ZnMnNFs are easier to be degraded and modified. By using MCF-7 cancer cells, the cell capture efficiency of ZnMnNFs is up to 88.2%. Furthermore, by using citric acid, it is discovered that, by comparison with Mn oxide nanofibers, the cell release efficiency of ZnMnNFs is improved to 95.1% from 15.4%. In addition, the viability of released cells exceeds 90%. Lastly, the robustness of ZnMnNFs substrates is tested in peripheral blood from breast cancer patients (BCP) and colorectal cancer patients (CCP). Combined with fluorescence labeling, CTCs are confirmed to be isolated from all the clinical samples. This is the first trial of using ternary inorganic ESNFs for cancer cell capture. It is anticipated that the degradable ESNFs will provide biocompatible theranostic platforms and overcome the current limitations of cell release for high-precision gene analysis.

Establishment of a universal and sensitive plasmonic biosensor platform based on the hybridization chain reaction (HCR) amplification induced by a triple-helix molecular switch.

Herein, we established a universal and sensitive plasmonic sensing strategy for biomolecule assays by coupling the hybridization chain reaction (HCR) strategy and a triple-helix molecular switch. Upon the recognition of the target, a single-stranded DNA as a universal trigger (UT) was released from the triple-helix molecular switch (THMS). Thus, the HCR process can be triggered between two hairpins M1 and M2, resulting in the aggregation of gold nanoparticles (AuNPs) via the hybridization between the tail sequence on M1 (or M2) and a DNA-AuNP probe with a dramatic change in the absorbance at 521 nm. More specifically, the strategy, which was conducted by the introduction of target-specific recognition of THMS and universalized by virtue of altering the aptamer or DNA sequence without changing the triple-helix structure, enables simple design for multiple target detection. By taking advantage of THMS, this strategy could enable stable and sensitive detection of a variety of targets including nucleic acids, small molecules and proteins, which may possess great potential for practical applications.

Carbon quantum dots derived from the extracellular polymeric substance of anaerobic ammonium oxidation granular sludge for detection of trace Mn(vii) and Cr(vi).

Carbon quantum dots (CQDs) were synthesized via a hydrothermal method, in which extracellular polymeric substance (EPS) from anaerobic ammonium oxidation (anammox) granular sludge was used as a carbon precursor, while citric acid and ethylenediamine were applied as auxiliary carbon source and passivation agent, respectively. The synthesized CQDs, with orderly spherical shape and mean size of 7.15 nm, emitted blue fluorescent light under UV radiation of 365 nm. The CQDs had a high fluorescence yield (40.84%), with good water solubility and excellent spectroscopic properties. In addition, the CQDs exhibited selective, sensitive and distinctive fluorescence quenching behaviors for Cr(vi) and Mn(vii) in a PBS buffer solution (NaH2PO4-Na2HPO4) of pH 7, with a detection limit of 5.8 nM for Cr(vi) and 2.3 nM for Mn(vii). Owing to the nitrogen components from the EPS of anammox granules, the CQDs were well nitrogen-doped, promoting electron-transfer and leading to reduction between the CQDs and Mn(vii)/Cr(vi). These results indicate that CQD-based chemical sensing is a simple and efficient means for the fluorescence detection of Mn(vii) and Cr(vi).

Ectopic osteogenesis by type I collagen loaded with a novel synthesized PTH-related peptide-1 in vivo.

This study aims to investigate the ability of parathyroid hormone (PTH)-related peptide-1/type I collagen (PTHrP-1/Col-I) scaffold material to induce ectopic osteogenesis in the quadriceps muscle pocket of Sprague-Dawley (SD) rats. A novel peptide PTHrP-1 was derived from PTH and used at different concentrations (0, 0.1, 0.3, and 0.5 mg/ml) to induce ectopic osteogenesis. Radiographic examinations (X-ray, CT, and 3D reconstruction), pathological observations (H&E, Masson, Von Kossa, ALP and TRAP staining), immunohistochemical staining (Col-I, OCN and Runx-2 in tissues), western blotting was used to determine the qualitative and quantitative analysis of related markers proteins. Results confirmed that the appropriate concentration of PTHrP-1 can effectively enhance the osteogenic activity, thereby improving the positive results and protein expression of osteogenic markers (COL-I, OCN, and Runx-2) in the quadriceps muscle pocket of SD rats. Through qualitative and quantitative analysis, high concentration of PTHrP-1 promotes osteogenic activity and active bone resorption. This study confirmed that PTHrP-1 is a novel small molecule bioactive peptide, and the rat tail collagen scaffold is a good carrier of PTHrP-1 with excellent biocompatibility. The PTHrP-1/Col-I composite scaffold material is an effective substitute for bone tissue engineering and can effectively induce and promote bone formation in the quadriceps muscle pocket of rats. In addition, the promoting ability for osteogenic differentiation of 0.3 mg/ml PTHrP-1/Col-I composite scaffold material group was significantly better than that of 0, 0.1 and 0.5 mg/ml PTHrP-1/Col-I composite scaffold material groups. Hence, the optimal concentration of PTHrP-1 to promote ectopic osteogenesis is 0.3 mg/ml.