Search

In this study, an investigation on the influences of different manufacturing techniques on the heat transfer and pressure drop in the developing and fully developed regions of mini-tube under different flow regimes is introduced. The purpose of this research is to experimentally investigate the heat transfer and pressure drop characteristics using 3D-printed tubes and traditional stainless steel tubes in the vertical direction under isothermal and non-isothermal boundary conditions. Experiments are conducted using distilled water (Prandtl numbers varying from 4 and 7) at Reynolds numbers of 800-10000 with heat fluxes between 30 and 500 kW·m-2. Test tubes with inside diameters of 2 mm are used, and the average surface roughness is 1.6 μm and 15.3 μm, respectively. The results are compared with previous studies. It is verified that the heat transfer characteristics are almost the same for the traditional tube and the 3D-printed tube in the laminar region. The average deviation between these two tubes is 7.7%. However, for the turbulent region, the Nusselt numbers of 3D-printed tube in the turbulent region increases by an average of 45% as compared with a traditional tube. The friction factors under heating conditions also increased by an average of 209%. In addition, the 3D-printed tube enters the transition region earlier. The results show that the average critical Reynolds number of a traditional tube and 3D-printed tube is around 2300 and 2000, respectively. Correlations in the turbulent region are developed to predict the friction factors and heat transfer coefficients with good accuracy.

Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB).To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB.A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness.High TGR predicted both poor progression-free survival and overall survival (both P.001). In addition, TGR was associated with postoperative neurological dysfunction (P.001), Enneking staging (P = .016), denosumab treatment responsiveness (P = .035), and the number of CD3+ (P.001), PD-1+ (P = .009), PD-L1+ (P.001), and FoxP3+ tumor-infiltrating lymphocyte (P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB.These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients.

There are several treatment options for patients with concomitant carotid and coronary artery disease, and it is difficult to identify an optimal treatment strategy that has consensus. Here, we performed a meta-analysis to compare the early and long-term outcomes of staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches.We performed a meta-analysis that compared staged and synchronous carotid endarterectomy and coronary artery bypass grafting approaches between July 1976 and September 2021. PubMed, EMBASE, and the Cochrane Library were systematically searched for related articles.Nineteen studies were identified with a total of 39,269 and 30,066 patients in the synchronous and staged groups, respectively. Early mortality was lower in the staged group than in the synchronous group (odds ratio OR 1.256, 95% confidence interval CI 1.006-1.569, P= P 0.05, IPatients treated with the synchronous approach had a significantly higher risk of early mortality, stroke, TIA, wound infection, and reoperation and a lower risk of myocardial ischemia than those treated with the staged approach. There was no significant difference in the long-term results between the 2 groups.

Background Biliary atresia (BA) is one of the main causes of neonatal end-stage liver disease. Without timely diagnosis and treatment, most children with BA will develop irreversible liver fibrosis within the first two months. While current theorized causes of BA include viral infection, immune disorders, and genetic defects, the comprehensive etiology is still largely unknown. Recently, biliatresone attracted much interest for its ability to induce BA in both zebrafish and mice, so we summarized the latest progress of biliatresone research in BA and tried to answer the question of whether it could provide further clues to the etiology of human BA. Data sources We conducted a PubMed search for any published articles related to the topic using search terms including “biliary atresia”, “biliatresone”, “GSH”, and “HSP90”. Relevant data were extracted from the original text or supplementary materials of the corresponding articles. Results Biliatresone had shown its unique toxicity in multiple species such as zebrafish and mice, and pathogenic factors involved included glutathione (GSH), heat shock protein 90 (HSP90) and the related pathways. In combination with epidemiological evidence and recent studies on the intestinal flora in biliary atresia, a new pathogenic hypothesis that the occurrence of biliary atresia is partly due to biliatresone or its structure-like compounds depositing in human body via vegetables or/and the altered intestinal flora structure can be tentatively established. Conclusions Based on the existing evidence, we emphasized that GSH and HSP90 are involved in the development of BA, and the maternal diet, especially higher vegetable intake of Asian women of childbearing age, accompanied by the altered intestinal flora structure, may contribute to the occurrence of biliary atresia and the higher incidence in the Asia group. However, the evidence from large sample epidemiological research is necessary.

Marine medaka (Oryzias melastigma) animal models play critical roles in environmental and human health by facilitating evaluation of pollutant toxicity and building of disease models. The fish gut microbiota contributes to host health and physiological metabolism, especially special bacterial strains and their functions in marine organisms. However, the distribution of the gut microbiota during medaka growth and development is still unclear, and successful generation of a germ-free (GF) marine medaka model has not been reported to date. In this study, we investigated the microbial composition with the major phyla and genera of marine fish at different life stages, as well as the isolated culturable intestinal bacteria, and then identified them by sequencing of the16S rRNA V3-V4 region. Importantly, the early stage model (larvae) of GF marine medaka without feeding and long-term (from juvenile to early adult stages) GF fish fed GF brine shrimp (Artemiasp.) were first generated. Moreover, the basic indexes and behavioral ability of GF fish showed weaker and delayed developmental changes compared to conventionally raised (CR) marine medaka at the same life stages. Notably, the significant differences in the histopathological characteristics of immune organs, intestinal tissues and the reproductive system were observed between GF and CR early-adult and adult fish. Furthermore, the transcriptomic profiles of the screened critical genes in signaling pathways in GF and CR marine medaka were also explored to illustrate the developmental impacts of the absence of the intestinal microbiota during the host growth. Comprehensively, our study provided novel insights into the intestinal microbiota distribution of CR fish during growth, and GF marine medaka from the larval to adult stagesviaGF fish food preparation. The histopathological and transcriptomic differences indicated the potential microbial regulation on growth, and application prospects of GF medaka fish models to clarify the relationships of intestinal bacterial functions to host health in the future.SignificanceThe generation and application of germ-free (GF) fish models are mostly limited to the early life stages with innate immunity and without feeding. Marine medaka (Oryzias melastigma) is a critical animal for evaluating environmental toxicity and human disease models. The gut microbiota contributes to host growth and development, but GF model of this organism has not been successfully generated. In this study, we revealed for the first time the distribution of the gut microbiota in marine medaka during growth and generated GF fish from the larval to adult stages with GFArtemiaprovided daily as food. According to the basic indexes, weaker behavioral ability, smaller immune organs, reproductive system, intestinal tissues, and transcriptome, the delayed development and differences indicated the negative influences of the absence of the microbiota in GF medaka, compared to conventionally raised (CR) fish at the same life stages. All these results provided novel insights into the application of GF medaka models to define intestinal bacterial functions in the host.Graphical abstractThis work revealed the distribution of the gut microbiota in marine medaka during growth, and successfully generated GF marine medaka models from larvae to adults with GFArtemiaas food, which indicated the delayed development in the absence of the microbiota in GF fish. Moreover, the histopathological analysis presented further evidence of developmental differences in immune organs, intestinal villi, goblet cells, gonad tissues and cell maturation between GF and CR fish at various life stages. Finally, the transcriptomic profile showed the significantly differentially regulated genes, which combined with the major bacteria can be potential “biomarkers” to explore the inner mechanisms or signaling pathways of GF fish models for studying host development and health.

Background: Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC.Methods: All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed via survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC).Results: GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC.Conclusion: Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target.

In this study, cell and animal experiments proved that C-phycocyanin can inhibit the necroptotic signaling pathway by down-regulating RIPK1, RIPK3, and p-MLKL expression.

By employing accurate state‐of‐the‐art many‐electron quantum‐chemistry methods, we establish that monocyclic carbon rings can accommodate Li guest atoms. The low‐lying electronic states of these endocircular systems are analyzed and found to include both charge‐separated states where the guest Li atom appears as a cation and the ring as an anion and encircled‐electron states where Li and the ring are neutral. The electron binding energies of the encircled‐electron states increase drastically at their highly symmetric equilibrium geometries with increasing size of the ring, and in Li@C24, this state becomes the ground state. Li is very weakly bound vertical to the rings in the low‐lying encircled‐electron states, hinting to van‐der‐Waals binding. Applcations are mentioned., Endocircular Li carbon rings exhibit two types of electronic states of very different nature, the ordering of which changes with the ring size. This enables possible interesting applications by excitations from the electronic ground states to states of different nature depending on the ring size.

Giant cell tumor of bone is a highly invasive benign tumor with a high postoperative recurrence rate. Objective: This study aims to analyze the research hotspots and trends of global research on giant cell tumor of bone in the past 20 years, to provide a reference for relevant personnel in this field to carry out academic research. Methods: The literature related to giant cell tumor of bone from 2001 to 2021 was retrieved from the Web of Science. The bibliometrics research method and VOS Viewer were used to extract and analyze the keywords of the journal authors’ research institutions, and the research status and development direction in the recent 20 years were visualized. Results: A total of 2063 articles were included. The number of global publications is increasing every year. The United States contributes the most to global research, with the most citations and the highest H-index. The journal Clinical Orthopaedics and Related Research published the most articles on this issue. “Denosumab” and “h3f3a” will get more attention and be the next popular hotspot in the future. Conclusion: The study of giant cell tumor of bone is a hot spot of continuous development and has an important contribution to human health.

BACKGROUND: Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies and the relevant researches have shown controversial results. METHODS: Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models. RESULTS: Nine trials involving 4,112 patients were included in present meta-analysis. It was seen that hydroxychloroquine-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (OR 2.34, 95% CI 1.63-3.36) patients, however, it also showed benefits associated with the viral clearance in patients (OR 27.18, 95% CI 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely-infected COVID-19 patients (OR 0.27, 95% CI 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of >14 days follow-up period (OR 0.27, 95% CI 0.13-0.58) compared to ≦14 days follow-up period group that conversely showed an increased mortality rate (OR 2.09, 95% CI 1.41-3.10). CONCLUSION: Our results indicated that HCQ-AZI combination treatment increased mortality rate in COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely-infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale and long follow-up period studies in patients with COVID-19 are needed.

The low-lying electronic states of neutral X@C60 (X = Li, Na, K, Rb) have been computed and analyzed by employing state-of-the-art high level many-electron methods. Apart from the common charge-separated states, well known to be present in endohedral fullerenes, one non-charge-separated state has been found in each of the investigated systems. In Li@C60 and Na@C60, the non-charge-separated state is a caged-electron state already discussed before for Li@C60. This indicates that the application of this low-lying state of Li@C60 discussed before is also applicable for Na@C60. In K@C60 and Rb@C60, the electronic radial distribution analysis shows that this hitherto unknown non-charge-separated state possesses a different nature from that of a caged-electron state.

A novel class-E power amplifier (PA) using a current-injection (CI) technique is presented in this letter. An auxiliary current source, which injects the current into the load during each turn-off period of switching transistors, is introduced into the conventional class-E PA. Without the need of impedance transforming or increasing of the supply voltage, the proposed PA provides a new method to increase the output power. The proposed circuit is fabricated in a Taiwan Semiconductor Manufacturing Company’s (TSMC’s) 65-nm low power (LP) CMOS process. Measurement results show that the output power of the injected circuit reaches up to 14.12 dBm with a drain efficiency of 41% at 1.8 GHz. The output power improves more than 3 dB compared to the conventional class-E PA without CI.

Under the premise that financing constraints frequently occur in the supply chain, this paper investigates the financing model of the supplier providing guarantee for the retailer under symmetric and asymmetric information. The optimal solutions of the retailer, the supplier, and the bank are studied by using the Stackelberg game. Results show that increasing the supplier's guarantee proportion can effectively improve the bank's reasonable margin rate and increase the supplier's profit. Under the condition of asymmetric information, the bank can increase the probability of credit loan in the supply chain by reducing the cost of spot check and setting up a reasonable fine limit.

How local groundwater induces chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is still elusive. This study aims to elucidate the impacts of Sri Lanka's local groundwater in a CKDu prevalent area and reveal the possible pathogenic mechanism of CKDu using zebrafish models. The drinking water from the local underground well in Vavuniya was sampled and the water quality parameters including Na

The endocircular Li@C16 is a promising system as it can form both a charge-separated donor-acceptor complex and a non-charge-separated van der waals complex. By employing the state-of-the-art equation-of-motion coupled-cluster method, our study shows that the carbon ring of this system possesses high flexibility and may undertake large distortions. Due to the intricate interaction between the guest Li+ cation and the negatively charged ring, this system can form several isomers possessing different ground states. The interesting electronic structure properties indicate its applicability as a catalyst candidate in the future.

Background House dust mite (HDM)‐induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM‐induced AR risk. Methods Forty‐three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case‐control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM‐induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM‐induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut‐off value of total IgE for the diagnosis of HDM‐induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype‐Tissue Expression (GTEx) database. Results We found that rs754466 in DLG5 was significantly associated with a decreased HDM‐induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, p = 3.25 × 10−4, P FDR = 3.93 × 10−2). The rs754466 A allele reduced the risk of HDM‐induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. Conclusion Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM‐induced AR.

Psychological therapies are important for comprehensive chronic orofacial pain (COFP) treatment. This study is to validate the effects of psychological factors on oral health-related quality of life (OHRQoL) among COFP patients in China. Pain catastrophizing, which is a subjective cognitive emotion used to manage the psychological aspects of pain among COFP patients, was examined in relation to COFP severity and OHRQoL. All 479 participants were recruited in Changsha, Hunan Province, China. Cronbach’s alpha coefficients (0.868–0.960), composite reliability scores (0.924–0.969), and average variance extracted from each construct (0.555–0.753) all indicated a good model fit. Pearson’s correlation analysis showed that age and education status have a positive correlation with COFP severity, pain catastrophizing, and anxiety. COFP severity was related to anxiety, depression, and COFP-OHRQoL. Pain catastrophizing was related to employment status. Anxiety and depression symptoms indirectly mediated the correlation between COFP severity and COFP-OHRQoL. As a second-stage moderator, pain catastrophizing moderated the mediating effects of anxiety symptoms and depression symptoms. Our findings suggest that anxiety, depression, and pain catastrophizing should be evaluated jointly to improve COFP-OHRQoL among COFP patients. This evidence will help therapists to comprehensively treat patients for the best treatment effect.

The endocircular Li@C

The low-lying electronic states of neutral X@C60 (X = Li, Na, K, Rb) have been computed and analyzed by employing state-of-the-art high level many-electron methods. Apart from the common charge-separated states, well known to be present in endohedral fullerenes, one non-charge-separated state has been found in each of the investigated systems. In Li@C60 and Na@C60, the non-charge-separated state is a caged-electron state already discussed before for Li@C60. This indicates that the application of this low-lying state of Li@C60 discussed before is also applicable for Na@C60. In K@C60 and Rb@C60, the electronic radial distribution analysis shows that this hitherto unknown non-charge-separated state possesses a different nature from that of a caged-electron state.

Since COVID-19 outbreak, hydroxychloroquine (HCQ) has been tested for effective therapies, and the relevant researches have shown controversial results.Systematic review and meta-analysis were conducted after a thorough search of relevant studies from databases. Trials that have evaluated HCQ for COVID-19 treatment were recruited for statistical analysis with fixed- and random-effect models.Nine trials involving 4112 patients were included in present meta-analysis. It was seen that HCQ-azithromycin (HCQ-AZI) combination regimen increased the mortality rate in COVID-19 (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.63-3.36) patients; however, it also showed benefits associated with the viral clearance in patients (OR, 27.18; 95% CI, 1.29-574.32). HCQ-alone when used as a therapy in COVID-19 did not reveal significant changes in mortality rate, clinical progression, viral clearance, and cardiac QT prolongation. Subsequent subgroup analysis showed that HCQ treatment could decrease mortality rate and progression to severe illness in severely infected COVID-19 patients (OR, 0.27; 95% CI, 0.13-0.58). A lower risk of mortality rate was also noted in the stratified group of14 days follow-up period (OR, 0.27; 95% CI, 0.13-0.58) compared to ≤14 days follow-up period group that conversely showed an increased mortality rate (OR, 2.09; 95% CI, 1.41-3.10).Our results indicated that HCQ-AZI combination treatment increased mortality rate in patients with COVID-19, but it also showed benefits associated with viral clearance in patients. HCQ-alone used for treatment has revealed benefits in decreasing the mortality rate among severely infected COVID-19 group and showed potential to be used for COVID-19 treatment in long-term follow-up period group. Accordingly, more rigorous, large-scale, and long follow-up period studies in patients with COVID-19 are needed.

The inhibition effect of urea on ovalbumin (OVA) glycation was investigated, and the mechanism was evaluated through the changes in protein structure as well as glycation sites and average degree of substitution per peptide molecule (DSP) by conventional spectrometry and liquid chromatography-high resolution mass spectrometry (LC-HRMS). A urea concentration of 3 M was chosen as the optimum condition. Ultraviolet and fluorescence spectra suggested that both glycation and urea treatment could unfold the OVA, but urea inhibited the glycation-induced protein unfolding. Circular dichroism spectra showed that urea treatment could increase the β-sheet content and reduce the α-helix content of OVA. LC-HRMS indicated that the number of glycation sites was reduced from 15 to 3, and DSP values decreased with urea treatment. In conclusion, urea could significantly inhibit the OVA-glucose glycation, and the sites competition as well as structure unfolding inhibition resulted from urea could be the main factors.

To improve our knowledge of the factors regulating Phaeocystis globosa colony formation, the effects of the diatom Ditylum brightwellii on P. globosa colony development were investigated using co-culture and cell-free filtrate approaches. The co-culture experiments showed the moderate abundance of D. brightwellii significantly increased the number and size of colonies, whereas a dramatically decreased effect from high abundance of D. brightwellii. The low abundance of D. brightwellii promoted early formation of P. globosa colony. The cell-free filtrate experiments indicated that culture-filtrates from the exponential phase of D. brightwellii were stimulatory for P. globosa colony formation with more and bigger colonies formed, whereas an inhibitory effect from its senescence phase filtrates. D. brightwellii may influence P. globosa colony formation by regulating the growth of P. globosa solitary cells. Our results suggest that D. brightwellii influences P. globosa colony development, but its effects vary according to its concentrations and growth phases.

Determining the geometry of carbon rings is an ongoing challenge. Based on our calculations at a state-of-the-art level, we found that the C

The toxicity of Cr(VI) was widely investigated, but the defense mechanism against Cr(III) in bacteria are seldom reported. Here, we found that Cr(III) inhibited bacterial growth and induced reactive oxygen species (ROS). After exposure to Cr(III), loss of sodA not only led to the excessive generation of ROS, but also enhanced the level of lipid peroxidation and reduced the GSH level, indicating that the deficiency of Mn-SOD decreased the bacterial resistance ability against Cr(III). The adverse effects of oxidative stress caused by Cr(III) could be recovered by the rescue of Mn-SOD in the sodA-deficient strain. Besides the oxidative stress, Cr(III) could cause the bacterial morphology variation, which was distinct between the wild-type and the sodA-deficient strains due to the differential expressions of Z-ring division genes. Moreover, Mn-SOD might prevent Cr(III) from oxidation on the bacterial surface by combining with Cr(III). Taken together, our results indicated that the Mn-SOD played a vital role in regulating the stress resistance, expression of cell division-related genes, bacterial morphology, and chemistry valence state of Cr. Our findings firstly provided a more in-depth understanding of Cr(III) toxicity and bacterial defense mechanism against Cr(III).

BackgroundsSince COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis.MethodsA thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other.ResultsFive trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin. However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients.ConclusionThe use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective. The combination of hydroxychloroquine and azithromycin has shown synergic effects. However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.

This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol (PPOS) in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn't get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol (non-PPOS group), and underwent PPOS protocol (PPOS group) in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer (FET) in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone (bFSH), antral follicle count (AFC), duration and total dosage of gonadotropin (Gn), number of oocytes retrieved, intracytoplasmic sperm injection (ICSI) rate, fertilization rate, and cycle cancellation rate between the two groups (P>0.05). However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group (P

We report on high-level coupled-cluster calculations for the anion states of the smallest fullerene C20. Using the state-of-the-art EA-EOM-CCSD method we revealed that the C20- anion has five bound electronic states at the C20 neutral ground-state D3d equilibrium configuration. These are two pairs of 2Eu and 2A2u states and one 2A1g state. The binding energies vary from 2.05 eV for the most bound 2Eu state to

Background As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella , a worldwide destructive pest of economically major crops. Results Based on transcriptome sequencing, a total of 7.88 Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM ≥ 1) in the P . xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 ‘highly represented’ KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P . xylostella reproduction. Conclusions Our newly developed P . xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P . xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P . xylostella reproduction aimed at screening potential molecular targets for integrated pest management.

The development of small-molecule G-quadruplex DNA probes has attracted significant attention in recent years. However, G-quadruplexes can display a wide variety of topologies, which process different structures and functions. Therefore, selective discrimination one G-quadruplex structure over another is promising. Herein, we reported the design, synthesis and biological evaluation of a long-chain fatty amine functionalized triphenylamine-quinolinium conjugate 1b . Significant enhancement of the fluorescence intensity (over 180 fold) was observed when 1b bound with HRAS G-quadruplex DNA, while much weaker enhancements were presented in the presence of other G-quadruplexes (45–90-fold) and single/double-stranded DNAs (less than 20-fold), indicating 1b had an excellent selectivity to HRAS . The details of the interactions were investigated by UV–Vis, FID and CD analysis. The results show 1b could interact and stabilize HRAS structure mainly by π-π stacking binding mode. The introduced amine chain of the structure core was found to be better in the terms of inducing selectivity toward G-quadruplex structure. In addition, the application of 1b as a fluorescent agent for living cell imaging was also demonstrated.

In recent years, fullerenes, as rising stars in carbon clusters, have been widely applied in various fields of science and technology. The high electron affinity of fullerenes, due to unique geometric and electronic structures, leads to wide applications in many fields, e.g., organic solar cells, supercapacitors, catalyzers, and superconductive materials. Due to the difficulty to synthesize of carbon clusters and to determine their structures experimentally, researchers have paid much attention to the theoretical studies of their geometric and electronic structures. It is only recently that it became possible to apply state-of-the-art theoretical methods, e.g., equation of motion coupled cluster singles and doubles method for electron affinities (EA-EOM-CCSD) to these large molecular systems. With such high cost methods, the full picture of electronic states of the first known fullerene C60 has finally been revealed. Study of electronic structures of large molecular systems, such as fullerenes, has become a great challenge for modern theoretical and computational chemistry. This thesis is devoted to the theoretical study of the electronic states of fullerene anions (e.g., C20–) and fullerene derivatives, utilizing accurate approaches. The latter includes endohedral fullerenes (e.g., Li@C20 and Li@C60) and carbon rings (e.g., C20). To the best of our knowledge, our work is the first study on bound states of the C20– fullerene anion, employing accurate theoretical approaches. We find that the smallest fullerene anion C20–, can form one superatomic and a manifold of valence bound states. It indicates that possessing superatomic bound states is one of the common properties of fullerenes. We hope that this finding sheds light on the study of fullerenes applications in the future. Our theoretically estimated adiabatic electron affinity of the C20– fullerene, is consistent with the electron affinity obtained in the photoelectron experiment. It verifies the validity of the application of high accurate EA-EOM-CCSD method in studying electronic structures of fullerenes. The endohedral fullerenes, e.g., Li@C20 and Li@C60, have attracted great attention due to their enhanced properties compared to the parent fullerenes. Our research on Li@C20 shows that the smallest fullerene, i.e., C20, can steal valence electron from the guest Li atom and form a charge separated donor-acceptor system. The Coulomb effect of Li+ is to stabilize the bound states, both valence and superatomic. Noteworthy, due to their different nature, the stabilizing effect on valence states is stronger than on superatomic states. The extra electron density distribution of superatomic states of the charge separated endohedral system is more compact compared to that of the parent fullerene, while the distribution of valence states does not exhibit this behavior. Based on our calculations on Li@C60, we have found several excited states. Most of the electronic states are charge separated states, the appearance of Li+ stabilized the excited states of Li@C60 compared to those of the parent isolated anion without changing their characters, similarly to our finding for Li@C20. Importantly, for Li@C60 we reported a hitherto unknown non-charge-separated state, which we referred to as the caged-electron state. This state is neither a valence nor a superatomic state, since its extra charge density is mostly distributed at the center of the cage. We demonstrate that the caged-electron state is formed due to the large radius of the C60 cage, which reduces the Coulomb attraction effect between Li+ and the negative carbon cage of the endohedral fullerene. In much larger fullerenes, e.g., Li@C180, this state even becomes the ground state, due to the much weaker Coulomb attraction effect. It is a great example of the impact of the fullerene’s size on its electronic structures. Additionally, we have mentioned several possible applications of this new kind of state. Last but not least, we turn to the carbon ring as the isomer of fullerenes. Carbon rings are intriguing and elegant species, but determining their geometry is an ongoing challenge. We have performed geometry optimization, vibrational frequency calculations and potential energy surface scans, based on EA-EOM-CCSD. Our work reveals that, similar to its fullerene isomer, the C20– ring can possess several bound states, including one superatomic state. Moreover, our calculation shows a symmetry breaking of the C20– ring anion structure occurring upon attaching an electron to the neutral ring. The discussion of the possible symmetry breaking mechanisms indicates that the shrinking and distortion of the ring upon electron attachment leading to the symmetry breaking, is a result of the interplay between the symmetry breaking and the totally symmetric modes. The discussion enriches the palette of possible symmetry breaking phenomena in carbon clusters.

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on pyroptosis of macrophages and the underlying molecular mechanisms. RAW264.7 macrophages were treated with AGE-alb (1, 2, 4 and 6 g/L) and control albumin (C-alb, 4 g/L) for 24 h, or preincubated with MCC950 (1 μmol/L) for 1 h and then treated with AGE-alb (4 g/L) for 24 h. Cell viability and caspase-1 activity were measured by MTT and assay kits, respectively. Lactate dehydrogenase (LDH) activity and the levels of interleukin-1β (IL-1β) and IL-18 in media were detected. Cell death degree was evaluated by TUNEL and Hoechst 33342/PI staining. The protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), procaspase-1 and cleaved caspase-1 were assessed by Western blot. The results showed that AGE-alb treatment caused obvious decrease in cell viability and increases in LDH leakage and the percentages of TUNEL- or PI-positive cells in a concentration-dependent manner. Additionally, AGE-alb promoted IL-1β and IL-18 secretion, upregulated NLRP3 expression, and increased caspase-1 activity especially at the dose of 4 and 6 g/L. However, MCC950 (an NLRP3 inhibitor) pretreatment inhibited significantly the decrease in cell viability and the increases in LDH leakage and percentages of TUNEL- or PI-positive cells induced by AGE-alb. Furthermore, MCC950 attenuated obviously AGE-alb-induced IL-1β and IL-18 secretion and caspase-1 activation. These results indicate that AGE-alb may induce macrophage pyroptosis, and the mechanism is at least partially by activating NLRP3-caspase-1 pathway.

By employing large-scale high-level EA-EOM-CCSD calculations, we have computed and analyzed the low-lying states of neutral Li@C60. Apart from one state, all states are found to be charge-separated states of the type Li+@C60-. The new state is the first reported non-charge-separated state in endohedral alkali fullerenes. This caged-electron state is analyzed in detail. Arguments are given that in larger highly symmetric endohedral fullerenes the caged-electron state can be the electronic ground state of the system. HF and DFT calculations on Li@C180 indeed find that the caged-electron state is the ground state and that in its equilibrium geometry Li sits at the center of the cage. Applications are mentioned.

Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety.This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement.Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients.Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.

Chalcogenides are extensively studied as infrared nonlinear optical materials, while rare-earth-based ones are scarcely explored. Here, two ternary rare-earth sulfides Ho3GaS6 (1) and Er3GaS6 (2), are obtained by high-temperature solid-state reactions. They are isostructural and crystallize in the orthorhombic noncentrosymmetric space group Cmc21. Their structures can be described as rare earth–S bonds constructed 3D framework, providing tetrahedral cavities for Ga atoms. Their optical band gaps are determined to be 3.03 (1) and 3.08 (2) eV, and their powder samples have no infrared absorption peaks between 400 and 4000 cm–1. Size-dependent second-harmonic generation measurements suggest that both of them are phase-matchable, and have the effects around 0.4 and 0.6 times that of AgGaS2 for their 150–210 μm samples. The structure-property relationship is also studied by structural analysis and theoretical calculations.

Numerous pieces of evidence documented the importance of gut microbiota in regulating human health and evaluating the toxicity of environmental pollutants, which are closely related to the host health in various aspects, including nutrition, energy translation, metabolism, pathogen resistance, and immune function. A variety of environmental factors can disrupt gut microbiota and their functions, and inevitably cause immune diseases, obesity and diabetes. However, deciphering the inner mechanisms involved in the functional interaction of gut microbes with host health is still needed extensive investigations. This review focused on the essential roles of intestinal microbes in host-related diseases and highlighted the development and applications of germ-free (GF) animal models, mainly zebrafish. Moreover, the generation, immunity characters, advantages and challenges of GF zebrafish models were also summarized. Importantly, the composition and isolation of zebrafish gut bacteria for further application and toxicity evaluation of aquatic environmental pollutants were also discussed. In conclusion, GF zebrafish play irreplaceable roles in understanding the potential functions and responses of customized microbiota towards human and environmental health implications.

Ag2Se quantum dots (QDs) are novel fluorescent probes in the second near-infrared window with great imaging quality and biocompatibility. Surface modification is an essential step to disperse Ag2Se QDs into biological fluids, and endow Ag2Se QDs with diverse surface chemistry. However, the effect of surface chemistry on the biological behaviors and chemical fates of Ag2Se QDs has not been studied, which hinders the design of suitable Ag2Se QDs for biomedical applications. Here, the distribution, degradation, excretion and toxicity of 2-aminoethanethiol and mercaptopropionic acid coated Ag2Se QDs (denoted as QDs-MEA and QDs-MPA, respectively) were systematically investigated in mice for a 28-day observation period after a single intravenous injection. Ag2Se QDs with different surface chemistries displayed similar trends in all observations, such as fast blood clearance, main uptake in the liver and spleen, severe biotransformation, Ag excretion through feces, and low toxicity. The major different behaviors observed were the partially pulmonary deposition, the faster transformation at the initial stage, the lower excretion percentage, and the more obvious damage to the liver by QDs-MEA compared to QDs-MPA. The surface chemistry of Ag2Se QDs regulated their biological behaviors and chemical fates in vivo, and surface chemistry should be fully regarded when designing Ag2Se QDs for biomedical applications from the biosafety perspective.

The toxicity and accumulation of zinc oxide nanoparticles (ZnO-NPs), ZnO microparticles (ZnO-MPs) and Zn ions were evaluated after long-term feeding with zinc-replenished food (1600 mg zinc equivalent per kg food) for 270 consecutive days. It was difficult for ZnO-NPs, ZnO-MPs and Zn ions were difficult to pass through the intestine barrier, and most of them were excreted mainly through feces. The distribution results showed that there was no noticeable difference among the distribution profiles of ZnO-NPs, ZnO-MPs and Zn ions in mice. Zn accumulated only in the digestive tract organs after the exposure to all three samples. However, the biomedical parameters and pathological investigations showed liver lesions induced by ZnO-MPs, but fewer by ZnO-NPs or Zn ions. The reason for the remarkably low in vivo toxicity of ZnO-NPs is discussed. Our findings suggest that ZnO-NPs are relatively biocompatible as the nutritional additive at the commonly used dose.

Nanoparticles are regularly used as contrast agents in bioimaging. Unlike other agents such as composite materials, nanoparticles can also be used for treating as well as imaging disease. Here we synthesized lanthanide functionalized gold nanoparticles that can be used for both imaging and therapy in vivo . That is a multifunctional nanoplatform was developed based on a simple and versatile method, by incorporating 10-nm gold nanoparticles and lanthanide ions (Gd 3+ and Yb 3+ ), denoted as LnAu nanoparticles hereby. The LnAu nanoparticles were then surface-modified using a PEGylated amphiphilic polymer (C 18 MH-mPEG), and the resulting PEG modified LnAu nanoparticles (PEG-LnAu) display good monodispersion in water and good solubility in biological media. Due to the low toxicity in vitro and in vivo (as determined by a cell viability assay and histological and serum biochemistry analysis), the PEG-LnAu nanoparticles can be successfully applied to in vivo magnetic resonance imaging (MRI), in vivo computed tomography (CT) imaging and photothermal therapy (PTT) for tumor-bearing mice. Therefore, the present work developed an easy yet powerful strategy to combine lanthanide ions and gold nanoparticles to a unified nanoplatform for integrating bioimaging and therapy.

G-quadruplex (G4) DNAs have attracted considerable interest because of their important biological functions and medical applications. Searching for highly specific binding molecules is important for the basic research of G4 DNA, as well as the design of novel anticancer drugs. Previous, we have developed a quinolone-substituted triphenylamine probe (TPA-2b) with selectivity to G4 DNAs. Herein, we further designed and synthesized a hydroxyethyl functionalized derivative (TPA-3) and investigated the interactions with G4 DNAs and living cells. TPA-3 was found to express significant fluorescence enhancement upon its interaction with G4 DNAs while shows almost no response to non-quadruplex DNAs. The distinction can even be easily distinguished by the naked eye under UV light. The spectral analysis showed TPA-3 bound to G4 DNAs mainly through intercalative binding mode. CD study results indicated TPA-3 did not disturb the conformation of G4 structure. Cellular uptake assay suggested that TPA-3 could pass through membrane and enter living cells. Our results suggested the side chain of core structure could change the binding affinity to G4 DNAs, as well as the interaction with living cells. Thus, this study gives some clues to design new G4 DNA probes with high selectivity, sensitivity, and biological imaging applications.