Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer.

Cancer is one of the most serious malignant diseases, and chemotherapy is cancer's main clinical treatment method. However, chemotherapy inevitably produces drug resistance, and side effects accompany them. Adjuvant therapy is an effective way to enhance chemotherapeutic drug sensitivity and reduce side effects. This study found allicin, garlic's active ingredient, is an inhibitor of transmembrane protein 16A (TMEM16A), a novel drug target of lung adenocarcinoma. Allicin concentration-dependently inhibited TMEM16A currents with an IC50 of 24.35 ± 4.14 µM. Allicin thiosulfinate moieties bound with R535A/E624A/E633A residues of TMEM16A blocked the ion transport function and downregulated TMEM16A protein expression affecting the mitogen-activated protein kinase signal transduction. Then, allicin reduced the viability and migration of LA795 cells, and induced cell apoptosis. Moreover, multitarget combination administration results indicated that the therapeutic effect of 3.56 mg/kg allicin and 3 mg/kg cisplatin combined administration was superior to the superposition of the two drugs alone, demonstrating that the anticancer effects of allicin and cisplatin were synergistic. In addition, low-concentration combined administration also avoided the side effects of cisplatin in mice. Based on the good tumor suppressor effect and high biosafety of allicin and cisplatin combination in vivo, allicin can be used for food adjuvant therapy of cisplatin chemotherapy.

Development of Microsatellite Markers Based on Transcriptome Sequencing and Evaluation of Genetic Diversity in Swimming Crab (Portunus trituberculatus).

P. trituberculatus is an economically important mariculture species in China. Evaluating its genetic diversity and population structure can contribute to the exploration of germplasm resources and promote sustainable aquaculture production. In this study, a total of 246,243 SSRs were generated by transcriptome sequencing of P. trituberculatus. Among the examined 254,746 unigenes, 66,331 had more than one SSR. Among the different SSR motif types, dinucleotide repeats (110,758, 44.98%) were the most abundant. In 173 different base repeats, A/T (96.86%), AC/GT (51.46%), and ACC/GGT (26.20%) were dominant in mono-, di-, and trinucleotide, respectively. GO annotations showed 87,079 unigenes in 57 GO terms. Cellular process, cell, and binding were the most abundant terms in biological process, cellular component, and molecular function categories separately. A total of 34,406 annotated unigenes were classified into 26 functional categories according to the functional annotation analysis of KOG, of which "general function prediction only" was the biggest category (6,028 unigenes, 17.52%). KEGG pathway annotations revealed the clustering of 34,715 unigenes into 32 different pathways. Nineteen SSRs were identified as polymorphic and, thus, used to assess the genetic diversity and structure of 240 P. trituberculatus individuals from four populations in the Bohai Sea. Genetic parameter analysis showed a similar level of genetic diversity within wild populations, and the cultured population indicated a reduction in genetic diversity compared with wild populations. The pairwise FST values were between 0.001 and 0.04 with an average of 0.0205 (p < 0.05), suggesting a low but significant level of genetic differentiation among the four populations. Structure analysis demonstrated that the four populations were classified into two groups including the cultured group and other populations. The phylogenetic tree and PCA revealed that a vast number of samples were clustered together and that cultivated individuals were distributed more centrally than wild individuals. The findings contribute to the further assessment of germplasm resources and assist to provide valuable SSRs for marker-assisted breeding of P. trituberculatus in the future.

Two-layer model of coronary artery vasoactivity.

Since vascular tone is regulated by smooth muscle cells in the media layer, a multilayer mechanical model is required for blood vessels. Here, we performed biaxial mechanical tests in the intima-media layer of right coronary artery to determine the passive and active properties in conjunction with the passive properties of adventitia for a full vessel wall model. A two-layer (intima-media and adventitia) model was developed to determine the transmural stress and stretch across the vessel wall. The mean ± SE values of the outer diameters of intima-media layers at transmural pressure of 60 mmHg in active state were 3.17 ± 0.16 and 3.07 ± 0.18 mm at axial stretch ratio of 1.2 and 1.3, respectively, which were significantly smaller than those in passive state (i.e., 3.62 ± 0.19 and 3.49 ± 0.22 mm, respectively, P < 0.05). The inner and outer diameters in no-load state of intima-media layers were 1.17 ± 0.09 and 2.08 ± 0.09 mm, respectively. The opening angles in zero-stress state had values of 159 ± 21° for intima-media layers and 98 ± 15° for adventitia layers, which suggests a residual strain between the two layers. There were slightly decreased active circumferential stresses (<10%), but significantly decreased active axial stresses (>25%) in the intima-media layer compared with those in the intact vessel. This suggests that the adventitia layer affects vascular contraction. The two-layer analysis showed that the intima-media layer bears the majority of circumferential tensions, in contrast to the adventitia layer, while contraction results in decreased stress and stretch in both layers.

Epitaxial silicon dots self-assembled on aluminum nitride/Si (111).

Si nanoscale dots are synthesized on AlN/Si(111) by molecular beam epitaxy. A dot density of 2.2 × 10(11) cm(-2) with a mean radius of 5.6 ± 2.8 nm is obtained in Volmer-Weber growth mode. A double Si coverage leads to a decrease in dot density and increase in dot size. The dot orientations are [11[overline]0](Si) (or [1[overline]10](Si))//[112[overline]0](AlN) and (111)(Si)//(0001)(AlN), which are similar (or identical) to the orientation of AlN relative to the Si substrate.

Biaxial vasoactivity of porcine coronary artery.

The passive mechanical properties of blood vessel mainly stem from the interaction of collagen and elastin fibers, but vessel constriction is attributed to smooth muscle cell (SMC) contraction. Although the passive properties of coronary arteries have been well characterized, the active biaxial stress-strain relationship is not known. Here, we carry out biaxial (inflation and axial extension) mechanical tests in right coronary arteries that provide the active coronary stress-strain relationship in circumferential and axial directions. Based on the measurements, a biaxial active strain energy function is proposed to quantify the constitutive stress-strain relationship in the physiological range of loading. The strain energy is expressed as a Gauss error function in the physiological pressure range. In K(+)-induced vasoconstriction, the mean ± SE values of outer diameters at transmural pressure of 80 mmHg were 3.41 ± 0.17 and 3.28 ± 0.24 mm at axial stretch ratios of 1.3 and 1.5, respectively, which were significantly smaller than those in Ca(2+)-free-induced vasodilated state (i.e., 4.01 ± 0.16 and 3.75 ± 0.20 mm, respectively). The mean ± SE values of the inner and outer diameters in no-load state and the opening angles in zero-stress state were 1.69 ± 0.04 mm and 2.25 ± 0.08 mm and 126 ± 22°, respectively. The active stresses have a maximal value at the passive pressure of 80-100 mmHg and at the active pressure of 140-160 mmHg. Moreover, a mechanical analysis shows a significant reduction of mean stress and strain (averaged through the vessel wall). These findings have important implications for understanding SMC mechanics.