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Background: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. Methods: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. Results: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). Conclusions: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.

Rhizosphere microorganisms can greatly affect plant growth, especially the plant growth-promoting rhizobacteria (PGPR), which can improve plant root development and growth because they contain various biological functions including nitrogen fixation, phosphate solubilization, and phytosiderophore production. This study demonstrates that Cyperus rotundus L. is capable of developing and forming complex underground reproductive systems at arbitrary burial depths and cutting modes due to its extremely strong multiplication and regeneration ability. With the densities of C. rotundus increasing, the abundance of PGPR, soil enzymes invertase and urease, the nutrient contents of the field soil, and maize quality were impacted. Notably, more abundance of PGPR-most notably, the nitrogen-fixing microorganisms (NFMs) such as Azospirillum, Burkholderia, Mycobacterium, and Rhizobium-enriches in the rhizosphere of C. rotundus than in that of maize. In addition, the activities of soil enzymes invertase (S_SC) and urease (S_SU) were significantly higher in its rhizosphere than in maize, further proving that more NFMs enrich the C. rotundus rhizosphere. The nutrient contents of the field soil of TN, SOM, and SOC were reduced, indicating that the presence of C. rotundus made the soil infertile. Hence, these pieces of evidence indicate that C. rotundus may drive the field soil infertile as reflected by reduced soil nutrients via altering rhizosphere bacteria community structure.

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, Prmt1 depletion promotes PrE gene expression in mouse embryonic stem cells (ESCs). Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in mESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Second, the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Most importantly, an embryonic chimeric assay showed that Prmt1 inhibition and mutated Klf4 at Arg 396 induce the integration of mouse ESCs into the PrE lineage. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.

The development of science and technology and the increasing demand of rehabilitation have driven the integration between artificial intelligence and rehabilitation medicine.In this study,statistical methods,document visualization tools,and other analysis methods were used in the Citespace software to analyze China's research status of artificial intelligence in the field of rehabilitation medicine with the key words of co-occurrence,emergence,and clustering.The relevant research hot spots were then classified and expounded.The results demonstrated that the current hot spots of artificial intelligence related to rehabilitation medicine included robots,brain-computer interfaces,human-computer interaction,and motor imagery.According to the clustering of key words and literature analysis,the five themes of artificial intelligence in rehabilitation medicine were determined as robot,brain-computer interface,intelligent rehabilitation training system,human-computer interaction,and assisted diagnosis and remote rehabilitation.Robotics and human-computer interaction would still be the research hot spots in the long future,and brain-computer interfaces,motor imagery,and remote rehabilitation would be new ones.This study analyzed the current hot spots,predicted the development trends,discussed the limitations,and proposed suggestions,aiming to provide reference for other scholars focusing on the application of artificial intelligence in rehabilitation medicine.

BACKGROUND This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS CTCs were found in all PSCC blood samples, but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for non-invasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response.Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed.Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome.We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.

We report an angle-resolved photoemission spectroscopy study of the antiferromagnetic Kondo lattice $\mathrm{Ce}{\mathrm{Pd}}_{5}{\mathrm{Al}}_{2}$, focusing on the quasi-two-dimensional $k$-space nature of its Fermi surface and, tuning photon energy to the Ce $4d--4f$ on-resonance transition, the hybridization of the Ce $4f$ state. A strong shoulder feature on the ${f}^{0}$ peak was detected, suggesting hybridization between conduction and $f$ bands. On-resonance spectra revealed narrow, yet hybridized quasiparticle bands with sharp peaks and $\ensuremath{\sim}$ 9 meV energy dispersion near the Fermi energy ${E}_{F}$. The observed dispersive hybridized $f$ band can be well described by a hybridization-band picture based on the periodic Anderson model (PAM). Hence, the $4f$ electrons in $\mathrm{Ce}{\mathrm{Pd}}_{5}{\mathrm{Al}}_{2}$ display a dual nature, with both localized and itinerant features, but with dominantly localized character.

High-resolution angle-resolved photoemission spectroscopy and ultrafast optical pump-probe spectroscopy were used to study semimetallic $1T\ensuremath{-}{\mathrm{TiTe}}_{2}$ quasiparticle dispersion and dynamics. A kink and a flat band, having the same energy scale and temperature-dependent behaviors along the $\overline{\mathrm{\ensuremath{\Gamma}}}\text{\ensuremath{-}}\overline{M}$ direction, were detected. Both manifested at low temperatures but blurred as temperature increased. The kink was formed by an electron-phonon coupling. And the localized flat band might be closely related to an electron-phonon coupling. Ultrafast optical spectroscopy identified multiple distinct time scales in the 10--300 K range. Quantitative analysis of the fastest decay process evidenced a significant lifetime temperature dependence at high temperatures, while this starts to change slowly below $\ensuremath{\sim}100$ K where an anomalous Hall coefficient occurred. At low temperature, a coherent ${A}_{1}g$ phonon mode with a frequency of $\ensuremath{\sim}4.36$ THz was extracted. Frequency temperature dependence suggests that phonon hardening occurs as temperature falls and anharmonic effects can explain it. Frequency fluence dependence indicates that the phonons soften as fluence increases.

We studied the association of rectal dose with acute diarrhea in patients with gynecologic malignancies undergoing whole-pelvic (WP) intensity-modulated radiotherapy (IMRT). From June 2006 to April 2019, 108 patients with previous hysterectomy who underwent WP IMRT were enrolled in this cohort study. WP irradiation of 39.6&ndash, 45 Gy/22&ndash, 25 fractions was initially delivered to the patients. Common Terminology Criteria for Adverse Events (CTCAE) version 3 was used to evaluate acute diarrhea during radiotherapy. Small bowel volume at different levels of isodose curves (Vn%) and mean rectal dose (MRD) were measured for statistical analysis. The multivariate analysis showed that the MRD &ge, 32.75 Gy (p = 0.005) and small bowel volume of 100% prescribed (V100%) &ge, 60 mL (p = 0.008) were independent factors of Grade 2 or higher diarrhea. The cumulative incidence of Grade 2 or higher diarrhea at 39.6 Gy were 70.5%, 42.2%, and 15.0% (p &lt, 0.001) in patients with both high (V100% &ge, 60 mL and MRD &ge, 32.75 Gy), either high, and both low volume-dose factors, respectively. Strict constraints for the rectum/small bowel or image-guided radiotherapy to reduce these doses are suggested.

We use ultrafast optical spectroscopy to study the nonequilibrium quasiparticle relaxation dynamics of the iron-based superconductor KCa$_2$Fe$_4$As$_4$F$_2$ with $T_c=33.5$ K. Our results reveal a possible pseudogap ($\Delta_{PG}$ = 2.4 $\pm$ 0.1 meV) below $T^*\approx 50$ K but prior to the opening of a superconducting gap ($\Delta_{SC}$(0) $\approx$ 4.3 $\pm$ 0.1 meV). Measurements under high pump fluence real two distinct, coherent phonon oscillations with 1.95 and 5.51 THz frequencies, respectively. The high-frequency $A_{1g}$(2) mode corresponds to the $c-$axis polarized vibrations of FeAs planes with a nominal electron-phonon coupling constant $\lambda_{A_{1g}(2)}$ = 0.194 $\pm$ 0.02. Our findings suggest that the pseudogap is likely a precursor of superconductivity, and the electron-phonon coupling may play an essential role in the superconducting pairing in KCa$_2$Fe$_4$As$_4$F$_2$., Comment: 6 pages, 3 figure

Huangqi Chifeng Tang (HQCFT), a traditional Chinese formula of three herbs, has been used to treat cerebral infarction (CI). Saposhnikoviae Radix (SR) was designed as a guiding drug for HQCFT to improve its angiogenic and anti-inflammatory effects. In this study, TTC staining was used to detect the area of CI. H&E staining was used to detect the histopathologic changes in the cerebral tissue. Western blotting was performed to detect the protein expression of NLRP3, caspase 1, IL-1β, IL-6, TNF-α, MMP-9, VEGF, and VEGFR2 in cerebral tissue. Immunohistochemistry was used to detect the protein expression of MMP-9, VEGF, and VEGFR2. The contents of HIF-1α, NLRP3, caspase 1, IL-1β, IL-6, and TNF-α in the serum were determined by ELISA. Our study showed that HQCFT and HQCFT-SR could improve the pathological condition and reduce the infarcted area of the brain tissue in a rat model. In addition, HQCFT and HQCFT-SR significantly decreased the expression levels and serum contents of NLRP3, caspase 1, IL-1β, IL-6, and TNF-α; increased the expression levels of the VEGF and VEGFR2 proteins; and obviously reduced the serum content of HIF-1α. Importantly, the cytokines in brain tissue and serum from the HQCFT group exhibited better efficacy than those from the HQCFT-SR group. HQCFT exerted significant angiogenic and anti-inflammatory effects in rats subjected to middle cerebral artery occlusion (MCAO); these effects can be attributed to the guiding and enhancing effect of SR.

Patients with familial type 17 of Parkinson’s disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson’s disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/β-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/β-catenin pathway. Protein levels of Wnt1 and nuclear β-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear β-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/β-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.

A large number of ecdysteroid-regulated 16 kDa proteins (ESR16s) of insects have been isolated and annotated in GenBank; however, knowledge on insect ESR16s remain limited. In the present study, we characterized an ecdysteroid-regulated 16 kDa protein gene isolated in Chinese oak silkworm, Antheraea pernyi Guérin-Méneville (‘ApESR16’ in the following), an important silk-producing and edible insect. The obtained cDNA sequence of ApESR16 is 1,049 bp, harboring an open reading frame of 441 bp that encodes a polypeptide of 146 amino acids. CD-search revealed that ApESR16 contains the putative cholesterol/lipid binding sites on conserved domain Npc2_like (Niemann–Pick type C-2) belonging to the MD-2-related lipid-recognition superfamily. Sequence comparison revealed that ApESR16 exhibits 51–57% identity to ESR16s of lepidopteran insects, 36–41% identity to ESR16 or NPC2a of nonlepidopteran insects, and 28–32% identity to NPC2a of vertebrates, indicating a high sequence divergence during the evolution of animals. Phylogenetic analysis found that the used sequences were divided into two groups corresponding to vertebrates and invertebrates, and the used insect sequences were also well clustered according to their families. The A. pernyi ESR16 mRNA is expressed during all four developmental stages and in all tested tissues. Injection of 20-hydroxyecdysone (20-E) into A. pernyi diapausing pupae triggering diapause termination induced upregulation of ESR16 mRNA compared to the diapausing pupae, with the highest expression level at day 2 in the ovaries but day 12 in the fat body. Our results suggested that ApESR16 might be a diapause-related gene and plays a vital role in the pupal diapause of A. pernyi.

High-quality large 1T phase of TiX 2 (X = Te, Se, and S) single crystals have been grown by chemical vapor transport using iodine as a transport agent. The samples are characterized by compositional and structural analyses, and their properties are investigated by Raman spectroscopy. Several phonon modes have been observed, including the widely reported A 1g and Eg modes, the rarely reported Eu mode (∼183 cm−1 for TiTe2, and ∼185 cm−1 for TiS2), and even the unexpected K mode (∼85 cm−1) of TiTe2. Most phonons harden with the decrease of temperature, except that the K mode of TiTe2 and the Eu and “A 2u /Sh” modes of TiS2 soften with the decrease of temperature. In addition, we also found phonon changes in TiSe2 that may be related to charge density wave phase transition. Our results on TiX 2 phonons will help to understand their charge density wave and superconductivity.

Itol A, a novel isoryanodane diterpene derived from Itoa orientalis Hemsl., has potent activities against insect pests. This study was conducted to determine the contact toxicity and biochemical effects of itol A on the Nilaparvata lugens. After macropterous females of N. lugens were exposed to itol A from 0.5 to 24 h, the mortality and poisoning symptoms were measured. Effects of itol A on the major enzymes activity and oxidative stress level were assessed in dose-response (with LD10-LD70 at 24 h) and time-course (with LD50 at 0.5–24 h) experiments for the potential toxicity mechanisms. Based on the results, the mortality of N. lugens showed significant dose- and time-dependent effects, with the 24-h LD50 value was 0.58 μg/insect. The symptoms of excitation, convulsion and paralysis were also observed. However, acetylcholinesterases (AChE) activity was not altered after itol A treatment compared to control. Na+/K+-ATPases, Ca2+-ATPases, Ca2+/Mg2+-ATPases, glutathione S-transferases (GSTs), cytochrome P450 monooxygenases (P450s), superoxide dismutases (SOD) and catalases (CAT) activities were significantly reduced in dose-response and time-course experiments. While acid phosphatases (ACP) and glutathione peroxidases (GPX) activities were significantly increased. We further revealed that itol A exposure resulted in the decrease of GSH/GSSG (reduced to oxidized glutathione) ratio and the increase of hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels in both experiments. The results indicated that the inhibition of Na+/K+-ATPases, Ca2+-ATPases, Ca2+/Mg2+-ATPases, GSTs, P450s, SOD and CAT activities and the induction of oxidative stress was one of the potential biochemical mechanisms of itol A against N. lugens.

Two new tetranuclear gadolinium clusters, [Gd4(μ3-OH)2(L1)6(beac)4] (1) and [Gd4(μ3-OH)2(L2)6(tmhd)4] (2) (HL1 = 5-(3-chlorobenzylidene)-8-hydroxylquinoline, HL2 = 5-(2-thenylidene)-8-hydroxylquinoline, beac = 1-benzoylaceton, tmhd = 2,2,6,6-tetramethyl-3,5-heptanedione), have been synthesized, then structurally and magnetically characterized. The X-ray structural analysis showed that both clusters 1 and 2 contain one Gd4 center with a rhombus-shaped arrangement, and all of the Gd(III) ions are located in a distorted square-antiprismatic coordination sphere. Magnetic property measurements indicate that 1 and 2 show magnetic refrigeration with −ΔSm = 20.43 J kg−1 K−1 for ΔH = 7 T at 2.0 K for 1 and −ΔSm = 19.94 J kg−1 K−1 for ΔH = 7 T at 2.5 K for 2.

Three new phenoxo-O-bridged dinuclear lanthanide(III) compounds, [Dy(bfa)2L1]2 (1), [Gd(hfac)3L2]2·C6H14 (2) and [Tb(hfac)3L2]2 (3) (bfa = benzoyltrifluoroacetone, hfac = hexafluoroacetylacetonate, HL1 = 2-[(3,4-dimethylaniline)-imino]methyl]−8-hydroxyquinoline and HL2 = 5-(2-thenylidene)-8-hydroxylquinoline), have been synthesized, then structurally and magnetically characterized. The X-ray structural analysis shows that 1–3 are phenoxo-O-bridged dinuclear compounds and the central eight-coordinated Ln(III) ions are in a slightly distorted dodecahedral geometry. Magnetic measurements indicated that slow magnetic relaxation behaviors were observed in 1 with an energy barrier (ΔE/kB) of 52.21 K and τ0 = 1.75 × 10−7 s; compound 2, however, exhibited magnetic refrigeration with −ΔSm = 15.06 J kg−1 K−1 for ΔH = 7.0 T at 2.0 K.

A series of lanthanide based dinuclear compounds, namely, [Ln(bfa)2L]2 (Ln = Gd (1), Tb (2), and Dy (3), bfa = benzoyltrifluoroacetone and HL = 2-[5-methyl-1,2-oxazol-imino]methyl]-8-hydroxyquinoline), were synthesized by employing a multidentate 8-hydroxyquinoline Schiff base derivative ligands (HL) and a bidentate β-diketonate coligand (bfa). The elemental analysis (EA), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), single-crystal X-ray diffraction and magnetic properties of the three Ln2 compounds were completely characterized. Structures of 1–3 are similar to each other with a parallelogram Ln2O2 core. Magnetic properties study indicates that 1 exhibits antiferromagnetic exchange interaction between two nearby GdIII centers and shows magnetic refrigeration (−ΔSm = 17.78 J kg−1 K−1 for ΔH = 7 T at 2.0 K). Ac magnetic susceptibility measurements of 3 demonstrate that slow relaxation behavior is observed in 3, with effective energy barrier Ueff = 24.3 K and pre-exponential factor τ0 = 1.71 × 10−6 s.

Bidens pilosa L. is a troublesome weed that affects the survival and production of crops. Our previous study showed that Brucea javanica (L.) residue has potent herbicidal activity against B. pilosa, and Bruceine D is the main active ingredient in the B. javanica residue. This study showed that Bruceine D significantly inhibited the germination of B. pilosa seeds, especially root hair, and it likewise showed a dose-dependent effect. Transcriptome results showed that phenylpropanoid biosynthesis was inhibited by Bruceine D (10 μg/mL). The expression of PAL, C4H, and 4CL genes were dynamic, whereas genes encoding COMT and POD remained significantly downregulated during Bruceine D treatment. The activities of these enzymes exhibited similar results. At the same time, the contents of several phenylpropanoid biosynthesis metabolites, including flavonoids and lignin, decreased in response to Bruceine D. Our results highlight the use of Bruceine D as a good candidate to develop bioherbicide.

We systemically investigate the nature of Ce 4f electrons in structurally layered heavy-fermion compounds CcmMnIn3m+2n (with M =Co, Rh, Ir, and Pt, m=l, 2, n=0 - 2), at low temperature using on-resonance angle-resolved photoemission spectroscopy. Three heavy quasiparticle bands f^0, f^1_7/2 and f^1_5/2 are observed in all compounds, but their intensities and energy locations vary greatly with materials. The strong f^0 states imply that the localized electron behavior dominates the Ce 4f states. The Ce 4f electrons are partially hybridized with the conduction electrons, making them have the dual nature of localization and itinerant. Our quantitative comparison reveals that the f^1_5/2 / f^0 intensity ratio is more suitable to reflect the 4f-state hybridization strength., Comment: 7 pages, 4 figures

Dirac semimetal PdTe 2 single-crystal temperature-dependent ultrafast carrier and phonon dynamics were studied using ultrafast optical pump-probe spectroscopy. Quantitative analysis revealed a fast relaxation process ( τ f ) occurring at a subpicosecond time scale originating from electron–phonon thermalization. This rapid relaxation was followed by a slower relaxation process ( τ s ) on a time scale of ∼ 7-9.5 ps which originated from phonon-assisted electron–hole recombination. Two significant vibrational modes resolved at all measured temperatures. These modes corresponded to in-plane ( E g ), and out-of-plane ( A 1 g ), Te atoms motion. Test results suggested that pure dephasing played an important role in the relaxation processes. Analysis of the electron–phonon coupling constant suggested that the A 1 g mode contributes greatly to the superconductivity, and high-frequency phonons are also involved forming of Cooper pairs. Our observations should improve the understanding of complex superconductivity of PdTe 2 .

Simple Summary Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma. Contrary to evaluating PD-L1 expression in tumor biopsy samples, this study assessed whether PD-L1 expression in circulating tumor cells (CTCs) can be a predictor of treatment response to PD-L1 inhibitors. The current study proved that there was no statistically significant correlation between the presence of PD-L1-positive CTCs and PD-L1 expression in tumor tissues. Moreover, PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Abstract Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.

This study investigated whether a self-designed assistive listening device (ALD) that incorporates an adaptive dynamic range optimization (ADRO) amplification strategy can surpass a commercially available monaurally worn linear ALD, SM100. Both subjective and objective measurements were implemented. Mandarin Hearing-In-Noise Test (MHINT) scores were the objective measurement, whereas participant satisfaction was the subjective measurement. The comparison was performed in a mixed design (i.e., subjects' hearing status being mild or moderate, quiet versus noisy, and linear versus ADRO scheme). The participants were two groups of hearing-impaired subjects, nine mild and eight moderate, respectively. The results of the ADRO system revealed a significant difference in the MHINT sentence reception threshold (SRT) in noisy environments between monaurally aided and unaided conditions, whereas the linear system did not. The benchmark results showed that the ADRO scheme is effectively beneficial to people who experience mild or moderate hearing loss in noisy environments. The satisfaction rating regarding overall speech quality indicated that the participants were satisfied with the speech quality of both ADRO and linear schemes in quiet environments, and they were more satisfied with ADRO than they with the linear scheme in noisy environments.

// Xiang-Me Lai 1 , Shu-Yu Liu 2 , Yi-Ta Tsai 3 , Guang-Huan Sun 2 , Sun-Yran Chang 2, 4 , Shih-Ming Huang 1, 3, 5 and Tai-Lung Cha 1, 2, 3, 5 1 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C 2 Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C 3 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, R.O.C 4 Buddhist Tzu Chi General Hospital, Taipei, Taiwan, R.O.C 5 Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, R.O.C Correspondence to: Tai-Lung Cha, email: tlcha@ndmctsgh.edu.tw Shih-Ming Huang, email: shihming@ndmctsgh.edu.tw Keywords: tyrosine kinase inhibitor, hypoxia-inducible factor, hypoxia associated factor, angiogenesis, renal cell carcinoma Received: April 07, 2017 Accepted: May 03, 2017 Published: May 17, 2017 ABSTRACT Anti-angiogenesis has emerged as a standard of care for metastatic renal cell carcinoma. However, long-lasting efficacy is seldom reached, and evasive resistance eventually occurs under anti-angiogenic tyrosine kinase inhibitor (TKI) therapy. To establish new therapeutic strategies, investigating the molecular mechanism of resistance is critically important. In our study, human umbilical vascular endothelial cells (HUVECs) were incubated with TKI treatment in conditioned medium derived from renal cancer cells (RCCs) to demonstrate cell viability. Quantitative real time PCR or Western blotting analysis detected the fluctuation of transcriptional factors HIF-1α and HIF-2α in RCCs under TKI treatment. We demonstrated the alteration of a specific cytokine produced from RCCs under normoxia or hypoxia incubation by utilizing a cytokine RT-PCR primer array. We found that the anti-angiogenic TKI sunitinib disrupted the balance between HIF-1α and HIF-2α in RCCs and led to a protective effect on HUVECs against sunitinib treatment when cultured with conditioned medium. Mechanistically, RCCs treated with sunitinib resulted in down-regulation of HIF-1α, but not HIF-2α, through reduction of both mRNA and protein levels. The down-regulation of HIF-1α by sunitinib occurred via hypoxia associated factor (HAF), which also enhanced HIF-2α transactivation activity to increase the production of pro-angiogenic factors and cytokines and promote HUVEC proliferation. This phenomenon was observed in ACHN and A498 cells, which express both HIF-1α and HIF-2α, but was not observed in 786-O cells, which express only HIF-2α. Our results illustrated that targeting both angiogenesis and hypoxia pathways might provide a resolution to dealing with the devastating effects of anti-angiogenesis resistance.

Aiming at mitigating urban climate issues, from the perspective of the correlation between the morphology of underlying surface and urban climate, based upon Xiamen's natural, economic and social conditions and urban development strategies, new approaches for compiling urban climate map for the coastal city in southeast Fujian province are explored. With the idea of problems-solving and cost-control, the approaches are anchored in the assessment of the differences between the theoretical value of urban climate issues distribution which are calculated with morphological zoning and corresponding observed results, therefore the main objective of climate analysis is redefined to locate areas where inappropriate constructions occur and map the city according with a hierarchy of carrying capacity of urban climate environment. Findings show that the Xiamen urban climate map produced with mentioned approaches may lay a foundation for generating customized urban design strategies along with providing quantitative analysis from urban climate research.

Background: The Support and Control in Birth (SCIB) scale primarily measures the perceived support and control of expectant mothers during childbirth, thereby obtaining an understanding of their birth experiences. The advantages of this scale are its good reliability and validity and that it consolidates birth support and control. However, a Chinese version of the scale has yet to be developed. Therefore, this study sought to evaluate the validity and reliability of a Chinese version of the Support and Control in Birth Scale (C-SCIB). Methods: A total of 228 postpartum women participated in this study. The C-SCIB scale was developed through a translation and back translation, followed by an evaluation of its content validity by a group of experts. Cronbach's α internal consistency and test-retest reliability were used to test the reliability of the scale. In addition, criterion-related validity (predictive validity and concurrent validity) and construct validity were used to test the validity of the scale.Results: The C-SCIB scale showed good results in terms of the item-level and scale-level content validity indices. The Cronbach's α internal consistency was 0.81, and its test-retest reliability was 0.96. The confirmatory factor analysis results showed the overall goodness-of-fit was parsimony fit indices. The predictive validity analysis showed a significant positive correlation between the C-SCIB scale and the Questionnaire Measuring Attitudes About Labor and Delivery (r =0.31, pr =0.49, p< 0.01) as well as the Labor Agentry Scale (r =0.51, p< 0.01).Conclusion: The C-SCIB scale was proven to have good reliability and validity, and thus can be used to measure the degree of support and the locus of control perceived by expectant women during labor.

To investigate the shared mechanisms of scutellarin in angina pectoris (AP) and ischemic stroke (IS) treatment.A network pharmacology approach was used to detect the potential mechanisms of scutellarin in AP and IS treatment by target prediction, protein-protein interaction (PPI) data collection, network construction, network analysis, and enrichment analysis. Furthermore, molecular docking simulation was employed to analyze the interaction between scutellarin and core targets.Two networks were established, including a disease-target network and a PPI network of scutellarin targets against AP and IS. Network analysis showed that 14 targets, namely, AKT1, VEGFA, JUN, ALB, MTOR, ESR1, MAPK8, HSP90AA1, NOS3, SERPINE1, FGA, F2, FOXO3, and STAT1, might be the therapeutic targets of scutellarin in AP and IS. Among them, NOS3 and F2 were recognized as the core targets. Additionally, molecular docking simulation confifirmed that scutellarin exhibited a relatively high potential for binding to the active sites of NOS3 and F2. Furthermore, enrichment analysis indicated that scutellarin might exert a therapeutic role in both AP and IS by regulating several important pathways, such as coagulation cascades, mitogen-activated protein kinase (MAPK) signaling pathway, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, Toll-like receptor signaling pathway, hypoxia inducible factor-1 (HIF-1) signaling pathway, forkhead box O (FoxO) signaling pathway, tumor necrosis factor (TNF) signaling pathway, adipocytokine signaling pathway, insulin signaling pathway, insulin resistance, and estrogen signaling pathway.The shared underlying mechanisms of scutellarin on AP and IS treatment might be strongly associated with its vasorelaxant, anticoagulant, anti-inflammatory, and antioxidative effects as well as its effect on improving lipid metabolism.

We present an investigation of the electronic structure of $1T\text{\ensuremath{-}}{\mathrm{TiTe}}_{2}$ single crystals using high-resolution angle-resolved photoemission spectroscopy utilizing tunable photon energy excitation. The typical semimetal-like electronic structure is observed and examined, where multiple hole pockets related to $\mathrm{Te}\phantom{\rule{0.28em}{0ex}}5p$ bands and one-electron pockets related to Ti $3d$ bands are populated by carriers. The obtained results reveal (i) a pronounced three-dimensional (3D) electronic band structure of $1T\text{\ensuremath{-}}{\mathrm{TiTe}}_{2}$ with typical semi-metallic features for both the Ti $3d$ and the $\mathrm{Te}\phantom{\rule{0.28em}{0ex}}5p$ states; (ii) multiple Fermi surface sheets and complex band structure; and (iii) an obvious kink in the dispersion at an energy of about 18 meV below the Fermi energy, which is an experimental observation of the kink structure in $1T\text{\ensuremath{-}}{\mathrm{TiTe}}_{2}$ single crystal. We find that this kink is induced by electron-phonon coupling in the material. These important and significant findings can help us to gain an in-depth understanding of the 3D electronic structure of semimetallic $1T\text{\ensuremath{-}}{\mathrm{TiTe}}_{2}$.

In this paper, Au nanoshell arrays, serving as a photo-activated material, are fabricated via the combination of self-assembled nanosphere lithography and the thermal decomposing polymer method. The intensity and position of surface plasmonic resonance can be tuned from the visible region to the near-infrared region by changing the size of Au nanoshell arrays. When resonance absorption peaks of metal nanoparticles are matched with emission wavelengths of core-shell CdSe/CdS quantum dots, fluorescent intensity of CdSe/CdS quantum dots can be strongly enhanced. The physical mechanism of fluorescent enhancement is explained.

The development of ratiometric fluorescence sensing platforms with simple synthetic routes and good anti-interference capacities are of great importance for their further application. Herein, hyperbranched polyethylenimine passivated carbon dots (HPEI-CDs) with concentration-modulated dual-excitation fluorescence property were synthesized. At a low concentration, HPEI-CDs only showed one fluorescence center, while at a relatively high concentration, its excitation peak around 355 nm would split into two peaks. Energy level splitting and broadening were demonstrated to be the origin of such dual-excitation behavior. Based on the dual-excitation signals, HPEI-CDs could serve as a ratiometric sensor for the detection of Fe3+ in aqueous solution. The assay exhibited a wide linear response concentration range (2–360 μM) with a limit of detection of 0.47 μM. Significantly, benefiting from the high concentration of HPEI-CDs, the sensor showed good selectivity and excellent anti-interference capacity. In addition, this nanosensor was successfully applied for the detection of Fe3+ in real water samples with satisfactory recoveries.