Macrophages-based immune-related risk score model for relapse prediction in stage I-III non-small cell lung cancer assessed by multiplex immunofluorescence.

Background: Macrophages are critical players in regulating innate and adaptive immunity in the tumor microenvironment (TME). The prognostic value of macrophages and their heterogeneous phenotypes in non-small cell lung cancer (NSCLC) is still uncertain. Methods: Surgically-resected samples of 681 NSCLC cases were stained by multiplex immunofluorescence to examine macrophage phenotypes as well as the expression levels of program death-ligand 1 (PD-L1) on them in both tumor nest and tumor stroma, including pan-macrophage (CD68+), M1 (CD68+CD163-), and M2 macrophages (CD68+CD163+). Various other immune cell markers, including CD4, CD8, CD20, CD38, CD66B, FOXP3, and CD133, were also evaluated. Machine learning algorithm by Random Forest (RF) model was utilized to screen the robust prognostic markers and construct the CD68-based immune-related risk score (IRRS) for predicting disease-free survival (DFS). Results: The expression levels of CD68 were moderately correlated with the levels of PD-L1 (P<0.001), CD133 (P<0.001), and CD8 (P<0.001). Higher levels of CD68 (OR 1.03, 95% CI: 1.01-1.05, P<0.001) as well as M1 macrophage (OR 1.04, 95% CI: 1.01-1.06, P<0.001) indicated shorter DFS. Despite without statiscial significance, intratumoral M2 macrophage (OR 1.05, 95% CI: 0.99-1.10, P=0.081) was also associated with worse DFS. IRRS incorporating three intratumoral CD68-related markers and four intrastromal markers was constructed and validated to predict recurrence (high-risk group vs. low-risk group: OR 2.52, 95% CI: 1.89-3.38, P<0.001). The IRRS model showed good accuracy [area under the curve (AUC) =0.670, 0.709, 0.695, 0.718 for 1-, 3-, 5-year, and overall DFS survival, respectively] and the predictive performance was better than the single-marker model (area under the curve 0.718 vs. 0.500-0.654). A nomogram based on clinical characteristics and IRRS for relapse prediction was then established and exhibited better performance than the tumor-node-metastasis (TNM) classification and IRRS system (C-index 0.76 vs. 0.69 vs. 0.60, 0.74 vs. 0.67 vs. 0.60, 0.81 vs. 0.74 vs. 0.60 of the entire, training, testing cohort, respectively). Conclusions: Our study suggested close interactions between CD68 and other immune markers in TME, demonstrating the prognostic value of CD68 in relapse prediction in resectable NSCLC.

Spectral analyses of Dy3+/Sr2+: LaF3 and Dy3+/Ca2+: LaF3 mixed crystals for laser applications.

Mixed crystals of Dy3+/Sr2+: LaF3 and Dy3+/Ca2+: LaF3 were grown by Bridgman technique and their spectral properties were investigated. Spectra broadening and peak shifts were observed, indicating the co-doping of Sr2+/Ca2+ brings about a more disordered local symmetry of Dy3+, which makes both crystals favorable for tunable lasing action. Low-temperature high resolution excitation and emission spectra were carried out for exploring the types of luminescent center of Dy3+ in crystals. Room-temperature absorption and emission spectra, together with the fluorescence decay curves were studied in both crystals for estimating their potentials for yellow and MIR lasers. Under 450 nm excitation, the largest emission cross-sections at 571 nm of 1.51 × 10-21 cm2 for Dy3+/Sr2+: LaF3 crystal and 1.56 × 10-21 cm2 for Dy3+/Ca2+: LaF3 crystal, along with the lifetimes of Dy3+: 4F9/2 level as 0.983 ms for Dy3+/Sr2+: LaF3 crystal, 1.143 ms for Dy3+/Ca2+: LaF3 crystal were obtained, respectively. Besides yellow emissions, MIR emissions approximately at 3 µm are more appealing. Under 1280 nm excitation, the largest emission cross-sections of 0.304 × 10-20 cm2 at 2885 nm in Dy3+/Sr2+: LaF3 crystal, and 0.319 × 10-20 cm2 at 2880 nm in Dy3+/Ca2+: LaF3 crystal, together with rather long lifetimes of Dy3+: 6H13/2 in the level of milliseconds were achieved, making them useful media for MIR lasers.

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Donor/Acceptor Properties of Aromatic Molecules in Complex Metal-Molecule Interfaces.

We present a comparative study, combining density functional theory with scanning tunneling microscopy/spectroscopy, of two aromatic molecules bonded with a variable number of Cu adatom(s) on a Cu(111) surface. The two molecules, 1,3,5-tris(pyridyl)benzene (TPyB) and 1,3,5-tris(4-radical-phenyl)benzene (TPB), possess the same aromatic backbone but bond weakly versus strongly to Cu with different terminal groups, respectively. We find that TPyB and TPB exhibit, respectively, small versus large charge transfers between the surface and the molecule; this contrast results in opposite shifts in the calculated density of states distributions and thus explains the opposite STS peak shifts observed in our experiments. The two molecules exhibit weak donor versus strong acceptor characters. This work provides a fundamental understanding, on a single-molecule level, of the principle that selecting specific functional groups can effectively and intentionally modify the molecular electronic properties in a wider class of molecule-metal interfaces.

Composition dependent reactivity of titanium oxide clusters.

Based on first-principles calculations of titanium oxide clusters, TinOm (n = 1-4), we reveal the composition dependent reactivity of titanium oxide clusters. Our interesting results include: (1) the reactivity depends on the ratio of O atoms in the clusters, with smaller O ratios associated with higher reactivity; (2) among the different titanium oxide species investigated, the most stable structures are TinO2n, but their reactivities are relatively lower than the clusters with a smaller O atom ratio; moreover, (3) when the O atom ratio is small, the reactivity required to form the Ti-Ti bond is larger than either the Ti-O or O-O bond between two interacting titanium oxide clusters. These results will be useful for designing efficient titanium oxide catalysts, or photocatalysts, in particular, for energy and environmental applications.

Ultrasensitive nonlinear absorption response of large-size topological insulator and application in low-threshold bulk pulsed lasers.

Dirac-like topological insulators have attracted strong interest in optoelectronic application because of their unusual and startling properties. Here we report for the first time that the pure topological insulator Bi2Te3 exhibited a naturally ultrasensitive nonlinear absorption response to photoexcitation. The Bi2Te3 sheets with lateral size up to a few micrometers showed extremely low saturation absorption intensities of only 1.1 W/cm(2) at 1.0 and 1.3 µm, respectively. Benefiting from this sensitive response, a Q-switching pulsed laser was achieved in a 1.0 µm Nd:YVO4 laser where the threshold absorbed pump power was only 31 mW. This is the lowest threshold in Q-switched solid-state bulk lasers to the best of our knowledge. A pulse duration of 97 ns was observed with an average power of 26.1 mW. A Q-switched laser at 1.3 µm was also realized with a pulse duration as short as 93 ns. Moreover, the mode locking operation was demonstrated. These results strongly exhibit that Bi2Te3 is a promising optical device for constructing broadband, miniature and integrated high-energy pulsed laser systems with low power consumption. Our work clearly points out a significantly potential avenue for the development of two-dimensional-material-based broadband ultrasensitive photodetector and other optoelectronic devices.

[Resonance scattering detection of trace Hg2+ using herring sperm DNA modified nanogold].

In pH 7.0 tris-HCl buffer solutions and in the presence of 0.017 mol x L(-1) NaCl, herring sperm DNA was combined with gold nanoparticles in size of 10 nm to form stable complex, and the NaCl did not cause the aggregation of the gold nanoparticles. Upon addition of Hg2+, that reacted with DNA to form more stable complex of Hg(2+)-DNA, and the gold nanoparticles aggregated to from larger nanogold clusters that led to considerable enhancement of the resonance scattering intensity at 572 nm enhanced considerably. The effect of GN concentration, DNA concentration, NaCl concentration, incubation time, and temperature, and ultrasonic irradiation was considered respectively, the conditions of 3.87 microg x mL(-1) GN, 11.7 microg x mL(-1) DNA, pH 7.0 Tris-HCl buffer solutions, 17 mmol x L(-1) NaCl, and incubation 10 min at 37 degrees C under the ultrasonic irradiation were chosen for use. Under the conditions, the enhanced resonance scattering intensity at 572 nm was linear to the Hg2+ concentration in the range of 3.3-3 333.3 nmol x L(-1), with regress equation of delta572 nm = 0.019c+5.0, coefficient of 0.999 1, and a detection limit of 2.5 nmol x L(-1) Hg2+. Results of interference tests showed that 30 micromol x L(-1) Mn2+, 33 micromol x L(-1) Mg2+ and Zn2+, 100 micromol x L(-1) Cd2+, 200 micromol x L(-1) Fe3+, and 420 micromol x L(-1) Mo6+, Pb2+ and Cu2+ did not interfered with the determination of 0.33 micromol x L(-1) Hg2+. That is, this resonance scattering spectral assay is of good selectivity. This assay was applied to the detection of Hg(II) in water sample, with a relative standard deviation of 5.1%, and the results were in agreement with that of the cool vapor atomic absorption spectrophotometry.

A topological transformation in evolutionary tree search methods based on maximum likelihood combining p-ECR and neighbor joining.

BACKGROUND: Inference of evolutionary trees using the maximum likelihood principle is NP-hard. Therefore, all practical methods rely on heuristics. The topological transformations often used in heuristics are Nearest Neighbor Interchange (NNI), Subtree Prune and Regraft (SPR) and Tree Bisection and Reconnection (TBR). However, these topological transformations often fall easily into local optima, since there are not many trees accessible in one step from any given tree. Another more exhaustive topological transformation is p-Edge Contraction and Refinement (p-ECR). However, due to its high computation complexity, p-ECR has rarely been used in practice. RESULTS: To make the p-ECR move more efficient, this paper proposes a new method named p-ECRNJ. The main idea of p-ECRNJ is to use neighbor joining (NJ) to refine the unresolved nodes produced in p-ECR. CONCLUSION: Experiments with real datasets show that p-ECRNJ can find better trees than the best known maximum likelihood methods so far and can efficiently improve local topological transforms in reasonable time.

[Study on the growth and spectral characteristics of LiNbO3:Cr:ZnO crystal].

The LiNbO3:Cr:ZnO crystals with the size up to phi20 mm x 50 mm were grown by the Czochralski technique. The absorption spectrum shows that there are two strong absorption wideband peaks and one weak absorption peak of to Cr3+ ion in the crystal. The peak values of the two strong absorption wideband peaks are 480 and 660 nm, which correspond to 4A2-->4 T1 and 4A2-->4 T2 transitions, respectively. The weak absorption peak at 727 nm corresponds to 4A2-->2 E(R line) transition; The fluorescence spectrum shows that one emission wideband peak ranging from 802 to 988 nm coexists with one weak emission peak at 754 nm corresponding to 4T2-->2 E transition. The peak value of emission wideband is at 871 nm, which corresponds to 4T2-->4A2 transition. The crystal field and Racah parameters were calculated, and Dq/B = 2.72 indicates that it has an stronger crystal field. The result shows that the wideband tunable laser can be obtained from this crystal because it not only has the necessary spectral characteristics required for tunable laser crystal but also has good physical chemical properties. Furthermore, the UV laser at about 420 nm can also be obtained from the crystal by its self-frequency doubling because it has a higher frequency-doubling coefficient.

[Crystal growth and spectroscopy of Er/Yb:KGW crystal].

The Er3 /Yb3+:KGW crystal with the dimensions of 30 mm x 25 mm x 15 mm was grown from K2W2O7 solvent by modified Czochralski method. The absorption spectrum was measured at room temperature and its absorption peaks were assigned. The emission spectrum was obtained under the excitation of 980 nm. There are two broad emission bands at 1024 and 1535 nm, whose FHWM are 60 and 36 nm respectively. It shows that this crystal is suitable for InGaAs LD pumping, and may be a promising laser crystal tunable at near 1 024 and 1 535 nm.

[Study on the growth and spectral characteristics of Cr3+: Al2 (WO4)3 crystal].

Cr3+:Al2(WO4)3 Crystal was grown from the Na2WO4 solvent system by using the TSSG method. The absorption spectrum shows that there are two strong absorption wideband peaks and one we ak absorption peak belonging to Cr3+ ion in the crystal. The peak values of two strong absorption wideband peaks are at 422 and 595 nm, respectively. The values of two weak absorption peaks are at 684 and 663 nm, respectively. The fluorescence spectrum shows that one emission wideband peak ranging from 650 to 820 nm coexists with one stronger emission peak at 680 nm. The peak value of emission wideband is at 740 nm. The crystal field and Racah parameters were calculated, where Dq/B = 2.420 indicates that it has an intermediary crystal field. The result shows that Cr3+:Al2(WO4)3 crystal is promising for tunable laser because it not only has the spectral characteristics required for tunable laser crystal but also has the good physicochemical properties.

[Study on the potentiation of bone marrow mesenchymal stem cells involved in sebaceous duct formation].

OBJECTIVE: To investigate the feasibility of differentiation of bone marrow mesenchymal stem cells (MSCs) into skin appandence. METHODS: Porcine MSCs were isolated from porcine marrow and grown in vitro. After labeling with BrdU, MSCs were engrafted to porcine skin. At 1, 2, 4 weeks after the transplantation, immunohistochemical examinations were carried out to detect the positive staining of BrdU and cytokeratin. RESULTS: A few sebaceous duct cells, which expressed cytokeratin, were also BrdU positive, and these cells were considered may to be transplanted MSCs-derived cells. CONCLUSION: Porcine MSCs might have the potential to differentiated into sebaceous duct cells in skin.

[Isolation and culture of multipotent mesenchymal stem cells from porcine bone marrow].

OBJECTIVE: To establish a method for the isolation of porcine mesenchymal stem cells (MSCs) from bone marrow and to demonstrate their differentiation ex vivo into various mesenchymal tissue cells. METHODS: MSCs were isolated from bone marrow and purified by centrifuge and in vitro. The proliferation and growth characteristics were observed in primary and passage culture. Cell cycle was analyzed by measuring DNA content with FAC-Scan flow cytometer and cell multipotent was identified with specific staining. RESULTS: The adherent, fibroblast-like cells were confluent in single layer after plating for 12-14 days. The cultured MSCs in vitro differentiated into osteoblasts. The cell cycle analysis showed that 80% of MSCs were in G0/G1 phase. CONCLUSION: Porcine MSCs can be isolated from postnatal bone marrow through their adherent ability. Porcine MSCs may be introduced as a valuable model system to study the mesenchymal lineages for basic research and tissue engineering.

[The up-conversion of frequency in Yb3+ :KGd(WO4)2 material].

By using the method of solid phase synthesis, a series of samples of KYbxGd(1 - x) (WO4)2 with different Yb3+ mole fraction of x = 0.03, 0.08, 0.10, 0.12, 0.15, 0.18, 0.20, 0.25, 0.28, respectively were synthesized when they were heated at 1,000 degrees C. Their fluorescence spectra were measured by using LD with a wavelength of 980 nm as the pumping source and RF-540 fluorescence spectrum measurement device. The weak fluorescence at 1,020 nm and strong blue fluorescence at 476 nm were obtained. Also, the relationship between the Yb3+ doping mole fraction and the fluorescence intensity at 476 nm was measured. The result indicates that the intensity of blue fluorescence increases rapidly with the increase of Yb3+ doping mole fraction and reaches the highest point at the Yb3+ doping mole fraction of 25%, then drops quickly with the increase of Yb3+ doping mole fraction. The result also indicates that the fluorescence intensity at 1,020 nm reaches the highest point when the Yb3+ doping mole fraction is about 8%-10%.

[Redistribution of epidermal stem cells in wound edge in the process of re-epithelialization].

OBJECTIVE: To study the redistribution of epidermal stem cells in regenerating wound tissues, and to elucidate the role of epidermal stem cells during wound repair. METHODS: 80 circular full-thickness wounds were produced on both sides of the back in 20 male Wistar rats (4 wounds in each animal). Then the 80 wounds were randomly divided into 2 groups: group A (treated with sulfadiazine silver- sulfadiazine zinc cream, n = 40) and group B (without any treatment, n = 40). The infection and healing process of the wounds were observed with naked eyes. Five mice were killed one time 3, 7, 14, and 21 days after the wounding. Two wounds with surrounding normal skin tissues were collected from each mouse. Routine histological examination was conducted with HE staining. Beta(1) integrin and keratin19 (K19), markers of epidermal stem cells, were employed to determine the distribution of epidermal stem cells with streptavidin-peroxidase (SP) immunohistochemical method. RESULTS: The healing rate of wounds was 80% (32/40) in group A, and 60% (24/40) in group B. No beta(1) integrin and K19 positive cells was found in the granulation tissue of all wounds in these 2 groups at any time point during the healing process. However, a few beta1 integrin and K19 positive cells, bearing no anatomic relation with the epidermal stem cells in the basal layer, were found scattering in the stratum spinosum and stratum granulosum of the epidermis on the wound edges. The closer to the wound the more concentrated the beta(1) integrin and keratin19 positive cells. Their numbers increased gradually along with the shrinking of the wound surface until the wound completely healed. The numbers of the beta(1) integrin and keratin19 positive cells decreased gradually after epithelialization. The numbers of the beta(1) integrin and keratin19 positive cells were obviously lower in the infected wounds than in the uninfected wounds. CONCLUSION: Epidermal stem cells participated in the healing of wound. The function of redistribution of epidermal stem cells in wound edges seems to promote the re-epithelialization of granulating wounds.

[An experimental study on the differentiation of bone marrow mesenchymal stem cells into vascular endothelial cells].

OBJECTIVE: To investigate the feasibility of differentiation of bone marrow mesenchymal stem cells (MSCs) into vascular endothelial cells and the mechanism of its involvement in wound healing. METHODS: Porcine MSCs were harvested from porcine marrow, and they were isolated and purified by density gradient centrifugation. After being cultured and amplified in vitro, the MSCs were labelled with BrdU (5-bromodeoxy-uridine). Full skin loss wound was created on the back of the mini-swine whose bone marrow was obtained. The labelled MSCs with fibrin glue as the vector were regrafted back to the donor animal wound. The wound tissue specimens were harvested at 2, 4, 6, 8 and 12 post-operation weeks and were immunohistochemically stained by BrdU and factor VIII (FVIII) for comparative study. RESULTS: Most BrdU positive cells aggregated around small blood vessels in the granulation tissue of the wounds. Only individual vascular endothelial cells were BrdU positive. There was FVIII expression in the cytoplasm of BrdU positive cells. CONCLUSION: MSCs were closely correlated with the formation of small blood vessels in granulation tissue during wound healing process. The porcine MSCs possessed the potential to differentiate into vascular entoehelial cells and to participate in wound healing under the micro-enviroment of the wound.