Group mating in Cretaceous water striders.

Fossilized mating insects are irreplaceable material for comprehending the evolution of the mating behaviours and life-history traits in the deep-time record of insects as well as the potential sexual conflict. However, cases of mating pairs are particularly rare in fossil insects, especially aquatic or semi-aquatic species. Here, we report the first fossil record of a group of water striders in copulation (including three pairs and a single adult male) based on fossils from the mid-Cretaceous of northern Myanmar. The new taxon, Burmogerris gen. nov., likely represents one of the oldest cases of insects related to the marine environment, such as billabongs formed by the tides. It exhibits conspicuous dimorphism associated with sexual conflict: the male is equipped with a specialized protibial comb as a grasping apparatus, likely representing an adaptation to overcome female resistance during struggles. The paired Burmogerris show smaller males riding on the backs of the females, seemingly recording a scene of copulatory struggles between the sexes. Our discovery reveals a mating system dominated by males and sheds light on the potential sexual conflicts of Burmogerris in the Cretaceous. It indicates the mating behaviour remained stable over long-term geological time in these water-walking insects.

Exploration of s new biomarker in osteosarcoma and association with clinical outcomes: TOP2A+ cancer associated fibroblasts.

BACKGROUND: Osteosarcoma (OS) is the leading malignant primary bone tumor in young adults and children and has a high mortality rate. Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment, influencing cancer progression and metastasis. However, there is no systematic study on the role of CAF in OS. METHODS: We collected six OS patients' single-cell RNA sequencing data from the TISCH database, which was processed using the Seurat package. We selected gene sets from the well-known MSigDB database and resorted to the clusterprofiler package for gene set enrichment analysis (GSEA). The least absolute shrinkage and selection operator (LASSO) regression model was used for identification of the variables. Receiver operating characteristic and decision curve analyses were utilized for determining the efficacy of the monogram model. RESULTS: TOP2A+ CAFs was recognized as the carcinogenic CAFs subset, given its intense interaction with OS malignant cells and association with the critical cancer driver pathway. We intersected the differentially expressed genes of TOP2A+ CAFs with the prognostic genes selected from 88 OS samples. The acquired gene set was selected using the LASSO regression model and integrated with clinical factors to obtain a monogram model of high prognosis predicting power (area under the curve of 5 year survival at 0.883). Functional enrichment analysis revealed the detailed difference between two risk groups. CONCLUSION: We identified TOP2A+ CAFs as a subset of oncogenic CAFs in OS. Based on differentially expressed genes derived from TOP2A+ CAFs, combined with bulk transcriptome prognostic genes, we constructed a risk model that can efficiently predict OS prognosis. Collectively, our study may provide new insights for future studies to elucidate the role of CAF in OS.

300 Million years of coral treaders (Insecta: Heteroptera: Hermatobatidae) back to the ocean in the phylogenetic context of Arthropoda.

Among hundreds of insect families, Hermatobatidae (commonly known as coral treaders) is one of the most unique. They are small, wingless predaceous bugs in the suborder Heteroptera. Adults are almost black in colour, measuring about 5 mm in body length and 3 mm in width. Thirteen species are known from tropical coral reefs or rocky shores, but their origin and evolutionary adaptation to their unusual marine habitat were unexplored. We report here the genome and metagenome of Hermatobates lingyangjiaoensis, hitherto known only from its type locality in the South China Sea. We further reconstructed the evolutionary history and origin of these marine bugs in the broader context of Arthropoda. The dated phylogeny indicates that Hexapoda diverged from their marine sister groups approximately 498 Ma and that Hermatobatidae originated 192 Ma, indicating that they returned to an oceanic life some 300 Myr after their ancestors became terrestrial. Their origin is consistent with the recovery of tropical reef ecosystems after the end-Triassic mass extinction, which might have provided new and open niches for them to occupy and thrive. Our analyses also revealed that both the genome changes and the symbiotic bacteria might have contributed to adaptations necessary for life in the sea.

Integrative metabolomics and network pharmacology to study the preventative impact of dioscin treatment on hyperuricemia.

This work aims to combine network pharmacology and metabolomics to explore the mechanism of action of dioscin on hyperuricemia (HUA). The preventative impact of dioscin on HUA and its putative mechanism were examined using network pharmacological analysis and metabonomics. Network pharmacology study further pointed out the potential targets of dioscin after a review of the relevant biomarker pathways discovered by metabolomic analysis. Molecular docking was then used to examine how the active chemicals interacted with the target proteins. The therapeutic effect of dioscin on HUA was shown to be mediated by 13 potentially important metabolites as a result of metabonomic research. Most of these metabolites are regulated after dioscin therapy to help patients recover. Based on network pharmacology, we identified 10 central genes, which is partly in agreement with metabolomics data. Using metabolomics and network pharmacology, this study investigated the primary targets and mechanisms of dioscin in the treatment of HUA. It is advantageous that dioscin has been developed as an additional drug for the treatment of HUA.

Protective role of PERK-eIF2α-ATF4 pathway in chronic renal failure induced injury of rat hippocampal neurons.

PURPOSE: Chronic renal failure (CRF) is associated with impairment of hippocampal neurons. This study investigated the effect of PERK-eIF2α-ATF4 pathway in CRF. METHODS: Rat CRF model was established and rat hippocampal neurons were separated. Xanthine Oxidase method, fluorescence spectrophotometry and flow cytometry were applied to detect superoxide dismutase (SOD) content, reactive oxygen species (ROS) level and apoptosis in hippocampal neurons, respectively. The levels of phosphorylated (p)-PERK, phosphorylated (p)-eIF2α, CHOP, Bax, C-Caspase-3 and Bcl-2 in rats were measured using Western blot. Then, the neurotoxicity of serum from CRF rats was assessed in rat hippocampal neurons after treatment with rat CRF serum and transfection with or without PERK overexpression or knockdown plasmid. RESULTS: SOD activity was reduced, while ROS level and apoptosis rate were increased in hippocampal tissues of CRF rats. PERK-eIF2α-ATF4 and apoptosis pathways were activated in CRF rats. Cells treated with serum from CRF rats showed increases in apoptosis rate and LDH and ROS levels, and decreases in cell viability and SOD activity. However, overexpressed PERK could reverse the cytotoxic effect of serum from CRF rats. PERK overexpression could enhance the activation of PERK-eIF2α-ATF4 pathway in hippocampal neurons induced by serum from CRF rats. Furthermore, PERK overexpression could alleviate the increases in CHOP, Bax, C-Caspase-3 expressions and the reduction of Bcl-2 expression in hippocampal neurons induced by serum from CRF rats. CONCLUSION: PERK-eIF2α-ATF4 pathway induced by increased endoplasmic reticulum stress may alleviate CRF-induced hippocampal neuronal damage.

Joint Design of Polar Coding and Physical Network Coding for Two-User Downlink Non-Orthogonal Multiple Access.

In this paper, we propose a joint polar coding and physical network coding (PNC) for two-user downlink non-orthogonal multiple access (PN-DNOMA) channels, since the successive-interference-cancellation-aided polar decoding cannot be optimal for finite blocklength transmissions. In the proposed scheme, we first constructed the XORed message of two user messages. Then, the XORed message was superimposed with the message of the weak User 2 for broadcast. By doing so, we can utilize the PNC mapping rule and polar decoding to directly recover the message of User 1, while at User 2, we equivalently constructed a long-length polar decoder to obtain its user message. The channel polarization and decoding performance can be greatly improved for both users. Moreover, we optimized the power allocation of the two users with their channel conditions by considering the user fairness and the performance. The simulation results showed that the proposed PN-DNOMA can achieve performance gains of about 0.4-0.7 dB over the conventional schemes in two-user downlink NOMA systems.

The earliest known brood care in insects.

Brood care enhances offspring fitness and survival by providing protection or feeding through parents (commonly by females). It has evolved independently multiple times in animals, e.g. mammals, birds, dinosaurs and arthropods, especially various lineages of insects, and has significant implications for understanding the emergence of sociality of insects. However, few fossil insects document such an ephemeral behaviour directly. New exceptional fossils of the water boatman Karataviella popovi from the Middle-Late Jurassic Daohugou biota (ca 163.5 Ma, northeastern China), with adult females bearing clutches of eggs on their left mesotibia, provide a unique brooding strategy (asymmetric egg-carrying behaviour) unknown in all extinct and extant insects. Our discovery represents the earliest direct evidence of brood care among insects, pushing back by more than 38 million years, indicating that relevant adaptations associated with maternal investment of insects can be traced back to at least the Middle-Late Jurassic, and highlighting the existence of diverse brooding strategies in Mesozoic insects. In addition, our discovery reveals that a specialized trawl-like filter-capture apparatus of K. popovi probably represents pre-adaptions originally used for trapping coeval anostracan (fairy shrimp) eggs for food.

Diversification of the phytophagous lineages of true bugs (Insecta: Hemiptera: Heteroptera) shortly after that of the flowering plants.

More than 95% of phytophagous true bug (Hemiptera: Heteroptera) species belong to four superfamilies: Miroidea (Cimicomorpha), Pentatomoidea, Coreoidea, and Lygaeoidea (all Pentatomomorpha). These iconic groups of highly diverse, overwhelmingly phytophagous insects include several economically prominent agricultural and silvicultural pest species, though their evolutionary history has not yet been well resolved. In particular, superfamily- and family-level phylogenetic relationships of these four lineages have remained controversial, and the divergence times of some crucial nodes for phytophagous true bugs have hitherto been little known, which hampers a better understanding of the evolutionary processes and patterns of phytophagous insects. In the present study, we used 150 species and concatenated nuclear and mitochondrial protein-coding genes and rRNA genes to infer the phylogenetic relationships within the Terheteroptera (Cimicomorpha + Pentatomomorpha) and estimated their divergence times. Our results support the monophyly of Cimicomorpha, Pentatomomorpha, Miroidea, Pentatomoidea, Pyrrhocoroidea, Coreoidea, and Lygaeoidea. The phylogenetic relationships across phytophagous lineages are largely congruent at deep nodes across the analyses based on different datasets and tree-reconstructing methods with just a few exceptions. Estimated divergence times and ancestral state reconstructions for feeding habit indicate that phytophagous true bugs explosively radiated in the Early Cretaceous-shortly after the angiosperm radiation-with the subsequent diversification of the most speciose clades (Mirinae, Pentatomidae, Coreinae, and Rhyparochromidae) in the Late Cretaceous.

Determining the relationship between cytokeratin expression and prognostic factors in human gastric cancer.

Determining the prognosis of gastric cancer is the most crucial step in the treatment process. Cytokeratins are intermediate filaments found in the intracellular structure of epithelial tissues. Recent researches have focused on determining the relationship between the expression of cytokeratins and the degree and prognosis of tumors. This study aimed to investigate the relationship between the incidence of cytokeratin-20 and cytokeratin-7 in patients with gastric carcinoma with factors influencing the prognosis. In this regard, the study was conducted cross-sectional. The expression of cytokeratin-20 and cytokeratin-7 was evaluated on 50 gastric adenocarcinoma specimens with different degrees of differentiation by the immunohistochemical method. We determined the relationship between the incidence of cytokeratin-20 and cytokeratin-7 with factors affecting the prognosis of patients, including the degree of differentiation of gastric cancer tissue, lymph node involvement, and the depth of tumor invasion. Data were statistically analyzed by Chi-square and Spearman tests. The results showed a statistically inverse relationship between the incidence of cytokeratin-20 and cytokeratin-7 with the degree of tissue differentiation and lymph node involvement in gastric cancer. Although there was a statistically significant relationship between the incidence of tissue invasion in gastric cancer and the incidence of cytokeratin-7, there was no association between the incidence of cytokeratin-20 and tissue invasion. In general, decreased cytokeratin-20 and cytokeratin-7 are associated with decreased tissue differentiation and increased lymph node involvement.

GJD Modulates Cardiac/Vascular Inflammation and Decreases Blood Pressure in Hypertensive Rats.

Gedan Jiangya decoction (GJD) (aqueous ethanol extract), a traditional Chinese medicine formula which contain six botanical drugs (Uncaria rhynchophylla (Miq.) Miq., Salvia miltiorrhiza Bunge, Pueraria lobata (Willd.) Ohwi, Eucommia ulmoides Oliv., Prunella vulgaris L., and Achyranthes bidentata Blume) was designed to treat hypertension; however, the underlying mechanism of action is unclear. This study aimed to determine the mechanisms of action of GJD in the treatment of hypertension in spontaneously hypertensive rats (SHR). Male SHRs were randomly divided into five groups: GJD doses were low (1.36 g/kg/d), medium (2.72 g/kg/d), and high (5.44 g/kg/d), captopril (13.5 mg/kg/d), and SHR groups, with Wistar-Kyoto rats (WKY) serving as the control. Every rat was gavaged once a day. The ALC-NIBP, a noninvasive blood pressure device, measured systolic (SBP) and diastolic (DBP) blood pressures. Six weeks following treatment, all rats were anesthetized. The blood samples were obtained from the abdominal aorta and then serum isolated to assess endothelin-1 and angiotensin II, interleukin-1beta, interleukin-6, and TNF-alpha. The left ventricular and thoracic aortas were taken for HE staining, immunohistochemistry, RT-qPCR, and western blot examination. Following GJD therapy, SBP and DBP were significantly lowered, as were serum levels of endothelin-1 and angiotensin II. The thickness of the left ventricular and thoracic aorta walls reduced, as did type I collagen, type III collagen, and alpha-SMA expression in the left ventricular and aortic tissues. The GJD treatment significantly reduced serum levels of the inflammatory markers interleukin-1beta, interleukin-6, and TNF-alpha. Furthermore, interleukin-1 beta, interleukin-6, TNF-alpha, TAK1, and NF-κB/p65 levels were significantly reduced in left ventricular and aortic tissues, whereas IkB-alpha levels were significantly elevated. GJD has a dose-dependent effect on all parameters. In conclusion, GJD has been shown to lower blood pressure, improve cardiovascular remodeling, and reduce inflammation via regulating NF-κB in SHRs.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Non-Planckian infrared emission from GaAs devices with electrons and lattice out-of-thermal-equilibrium.

With the downscaled device size, electrons in semiconductor electronics are often electrically driven out-of-thermal-equilibrium with hosting lattices for their functionalities. The thereby electrothermal Joule heating to the lattices can be visualized directly by the noncontact infrared radiation thermometry with the hypothetic Planck distribution at a single characteristic temperature. We report here that the infrared emission spectrum from electrically biased GaAs devices deviates obviously from Planck distribution, due to the additional contribution from non-equilibrium hot electrons whose effective temperature reaches much higher than that of the lattice (Te>Tl). The evanescent infrared emission from these hot electrons is out-coupled by a near-field metamaterial grating and is hence made significant to the total far-field emission spectrum. Resonant emission peak has also been observed when the electron hotspots are managed to overlap spatially with the optical hotspots at the grating resonance. Our work opens a new direction to study nonequilibrium dynamics with (non-Planckian) infrared emission spectroscopy and provides important implications into the microscopic energy dissipation and heat management in nanoelectronics.

Curved waveguides in silicon written by a shaped laser beam.

We demonstrate, for the first time, the direct writing of curved optical waveguides in monocrystalline silicon with curve radii from 2 mm to 6 cm. The bending loss of the curved waveguides is measured and a good agreement with theoretical values is found. Raman spectroscopy measurements suggest the formation of inhomogeneous amorphous and polycrystalline phases in the laser-modified region. This direct laser-writing method may advance fabrication capabilities for integrated 3D silicon photonic devices.

Loss of SPACA1 function causes autosomal recessive globozoospermia by damaging the acrosome-acroplaxome complex.

STUDY QUESTION: Is the sperm acrosome membrane-associated protein 1 (SPACA1) gene critical to human globozoospermia? SUMMARY ANSWER: The biallelic loss-of-function (variant of SPACA1) causes globozoospermia as a result of acrosome-acroplaxome complex damage. WHAT IS KNOWN ALREADY: SPACA1 expression decreases in patients with globozoospermia. Spaca1 gene-disrupted mice have abnormally shaped sperm heads that resemble those of human globozoospermia. STUDY DESIGN, SIZE, DURATION: We recruited a consanguineous family with two brothers affected by infertility as a consequence of globozoospermia. The semen analysis data and ART outcomes were collected. Exome sequencing (ES) was used to identify potential pathogenic variants. Protein-protein interaction (PPI) technologies and proteomic analysis were utilized to explore the pathogenic mechanism. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two globozoospermic brothers and their consanguineous parents were recruited to identify the potential pathogenic variant through ES. A homozygous nonsense variant in the SPACA1 gene in both brothers inherited from the heterozygous parents was identified. Twenty normal fertile males were recruited as controls. Sperm ultrastructure was observed with transmission electron microscopy. Western blotting was performed to measure SPACA1 expression level in the sperm from the patients. Mass spectrometry (MS) analyses were used to identify differentially expressed proteins and to investigate proteins that interact with SPACA1. Co-immunoprecipitation (co-IP), yeast two-hybrid (Y2H) and immunofluorescence colocalization assays were used to confirm the PPI. MAIN RESULTS AND THE ROLE OF CHANCE: A nonsense variant (NM_030960.2: c.53G>A; p. Trp18*) in the SPACA1 gene was identified as the pathogenic variant in a family with globozoospermia. Patient IV:1 and Patient IV:2 had a phenotype very similar to that of Spaca1 gene-disrupted mice. The nonsense variant in SPACA1 led to premature transcriptional termination in the signal peptide, which was confirmed by western blotting. MS-based proteomics analysis showed that eight interactors of SPACA1 were differentially expressed in the patients' sperm, including actin-like Protein 7A (ACTL7A), an important component of the acrosome-acroplaxome complex. The PPI of SPACA1 and ACTL7A was confirmed via co-IP and Y2H assays. Immunofluorescence showed that SPACA1 and ACTL7A colocalized in mature sperm, revealing that these proteins were coexpressed spatially. LIMITATIONS, REASONS FOR CAUTION: Given the rarity of globozoospermia, only two patients from one family harbouring the SPACA1 variant were found. Future studies should evaluate SPACA1 variants in larger cohorts to corroborate this finding. WIDER IMPLICATIONS OF THE FINDINGS: This study revealed that the SPACA1 gene was critical for globozoospermia, which expanded the spectrum of causative genes for globozoospermia. This study also provided evidence for ICSI clinical outcomes for patients with SPACA1-deficient globozoospermia, which may guide clinical treatment strategies. Furthermore, this study explored the pathogenesis of globozoospermia caused by SPACA1 deficiency. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Precision Medical Research of National Key Research and Development Program (2018YFC1002400), National Natural Science Foundation of China (81873724), and Natural Science Foundation of Shanghai (20ZR1472700). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Amniotic fluid-derived extracellular vesicles: characterization and therapeutic efficacy in an experimental model of bronchopulmonary dysplasia.

BACKGROUND AIMS: Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored. METHODS: Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD). RESULTS: Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model. CONCLUSIONS: The authors' results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.

Evolution of endemism on a young tropical mountain.

Tropical mountains are hot spots of biodiversity and endemism, but the evolutionary origins of their unique biotas are poorly understood. In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities. Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere. Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue' in montane biodiversity hot spots under climate change scenarios.

Different leaf-mediated deposition, absorbed and metabolism behaviors of 2,4-D isooctyl ester between Triticum aestivum and Aegilops tauschii Coss.

Tausch's goatgrass (Aegilops tauschii Coss.), is a major weed species, infesting wheat (Triticum aestivum) fields in China. 2,4-D isooctyl ester is widely used for broadleaf weed control and selected as a tool to study the differences between, A. tauschii and T. aestivum. In this study, we measured the growth responses of these species to 2,4-D isooctyl ester and found that T. aestivum was more sensitive to the herbicide than A. tauschii. To clarify the reasons for this difference, we measured the leaf-mediated deposition, absorption and metabolism of 2,4-D isooctyl ester and the expression of auxin receptor transport inhibitor response (TIR1) gene in T. aestivum and A. tauschii. The results indicated that the deposition of 2,4-D isooctyl ester droplets may be lower on A. tauschii than on T. aestivum, because of the increased contact angle and greater density of trichomes on the leaves of the former. A distinct increase in 2,4-D isooctyl ester uptake was detected in T. aestivum during the entire experimental period, and the rate was 2.2-fold greater than that in A. tauschii at 6 h after treatment. Compared with A. tauschii, T. aestivum exhibited a greater accumulation of primary metabolite 2,4-D in plants, which may be responsible for the different responses of the two species. Additionally, the absolute expression level of TIR1 was clearly greater in T. aestivum than that in A. tauschii. These data will be helpful to further understand the differences between T. aestivum and A. tauschii, which may provide a unique perspective for the development and identification of new target compounds that are effective against this weed species.

Benzophenanthridine alkaloids suppress lung adenocarcinoma by blocking TMEM16A Ca2+-activated Cl- channels.

An increasing amount of evidence suggests that transmembrane member 16A (TMEM16A)-encoded Ca2+-activated Cl- channels play a crucial role in regulating tumorigenesis. Therefore, specific and potent TMEM16A inhibitors have been proposed to potentially be useful for the treatment of cancer. During drug screening, we found that benzophenanthridine alkaloids (sanguinarine, sanguinarium chloride, sanguinarine nitrate, ethoxysanguinarine, chelerythrine, and dihydrosanguinarine) potently inhibited the recombinant TMEM16A current. The IC50 and Emax values for TMEM16A inhibition of six tested benzophenanthridine alkaloids were 5.6-12.3 µM and 77-91%, respectively. These benzophenanthridine alkaloids also significantly inhibited the endogenous TMEM16A currents and proliferation, migration, and induced apoptosis in LA795 lung adenocarcinoma cells. These data demonstrate that benzophenanthridine alkaloids are novel TMEM16A inhibitors and are potentially useful in specific cancer therapies. These findings also provide new insight for the development of TMEM16A inhibitors.

Modeling and improving the output power of terahertz master-oscillator power-amplifier quantum cascade lasers.

A model based on carrier rate equations is proposed to evaluate the gain saturation and predict the dependence of the output power of a terahertz master-oscillator power-amplifier quantum cascade laser (THz-MOPA-QCL) on the material and structure parameters. The model reveals the design rules of the preamplifier and the power extractor to maximize the output power and the wall-plug efficiency. The correction of the model is verified by its agreement with the experiment results. The optimized MOPA devices exhibit single-mode emission at ∼ 2.6 THz with a side mode suppression ratio of 23 dB, a pulsed output power of 153 mW, a wall-plug efficiency of 0.22%, and a low divergence angle of ∼6°×16°, all measured at an operation temperature of 77 K. The model developed here is helpful for the design of MOPA devices and semiconductor optical amplifiers, in which the active region is based on intersubband transitions.

Icotinib: efficacy in different solid tumors and gene mutations.

Icotinib is a first-generation inhibitor of epidermal growth factor receptor, which has been approved by the Chinese National Medical Products Administration, for the treatment of non-small cell lung cancer with epidermal growth factor receptor sensitive mutations. In addition, icotinib also shows moderate activity in other solid tumors driven by epidermal growth factor receptor, including non-small cell lung cancer with epidermal growth factor receptor rare non-resistant mutations, and esophageal cancer with epidermal growth factor receptor amplification or overexpression. This article reviews the efficacy of icotinib in different solid tumors with different epidermal growth factor receptor alterations.