OBOX regulates mouse zygotic genome activation and early development.

Zygotic genome activation (ZGA) activates the quiescent genome to enable the maternal-to-zygotic transition1,2. However, the identity of transcription factors that underlie mammalian ZGA in vivo remains elusive. Here we show that OBOX, a PRD-like homeobox domain transcription factor family (OBOX1-OBOX8)3-5, are key regulators of mouse ZGA. Mice deficient for maternally transcribed Obox1/2/5/7 and zygotically expressed Obox3/4 had a two-cell to four-cell arrest, accompanied by impaired ZGA. The Obox knockout defects could be rescued by restoring either maternal and zygotic OBOX, which suggests that maternal and zygotic OBOX redundantly support embryonic development. Chromatin-binding analysis showed that Obox knockout preferentially affected OBOX-binding targets. Mechanistically, OBOX facilitated the 'preconfiguration' of RNA polymerase II, as the polymerase relocated from the initial one-cell binding targets to ZGA gene promoters and distal enhancers. Impaired polymerase II preconfiguration in Obox mutants was accompanied by defective ZGA and chromatin accessibility transition, as well as aberrant activation of one-cell polymerase II targets. Finally, ectopic expression of OBOX activated ZGA genes and MERVL repeats in mouse embryonic stem cells. These data thus demonstrate that OBOX regulates mouse ZGA and early embryogenesis.

A vitamin-C-derived DNA modification catalysed by an algal TET homologue.

Methylation of cytosine to 5-methylcytosine (5mC) is a prevalent DNA modification found in many organisms. Sequential oxidation of 5mC by ten-eleven translocation (TET) dioxygenases results in a cascade of additional epigenetic marks and promotes demethylation of DNA in mammals1,2. However, the enzymatic activity and function of TET homologues in other eukaryotes remains largely unexplored. Here we show that the green alga Chlamydomonas reinhardtii contains a 5mC-modifying enzyme (CMD1) that is a TET homologue and catalyses the conjugation of a glyceryl moiety to the methyl group of 5mC through a carbon-carbon bond, resulting in two stereoisomeric nucleobase products. The catalytic activity of CMD1 requires Fe(II) and the integrity of its binding motif His-X-Asp, which is conserved in Fe-dependent dioxygenases3. However, unlike previously described TET enzymes, which use 2-oxoglutarate as a co-substrate4, CMD1 uses L-ascorbic acid (vitamin C) as an essential co-substrate. Vitamin C donates the glyceryl moiety to 5mC with concurrent formation of glyoxylic acid and CO2. The vitamin-C-derived DNA modification is present in the genome of wild-type C. reinhardtii but at a substantially lower level in a CMD1 mutant strain. The fitness of CMD1 mutant cells during exposure to high light levels is reduced. LHCSR3, a gene that is critical for the protection of C. reinhardtii from photo-oxidative damage under high light conditions, is hypermethylated and downregulated in CMD1 mutant cells compared to wild-type cells, causing a reduced capacity for photoprotective non-photochemical quenching. Our study thus identifies a eukaryotic DNA base modification that is catalysed by a divergent TET homologue and unexpectedly derived from vitamin C, and describes its role as a potential epigenetic mark that may counteract DNA methylation in the regulation of photosynthesis.

Which contributes more to the relict flora distribution pattern in East Asia, geographical processes or climate change? New evidence from the phylogeography of Rehderodendron kwangtungense.

BACKGROUND: Relict species are important for enhancing the understanding of modern biogeographic distribution patterns. Although both geological and climatic changes since the Cenozoic have affected the relict flora in East Asia, the contributions of geographical processes remain unclear. In this study, we employed restriction-site associated DNA sequencing (RAD-seq) and shallow genome sequencing data, in conjunction with ecological niche modeling (ENM), to investigate the spatial genetic patterns and population differentiation history of the relict species Rehderodendron kwangtungense Chun. RESULTS: A total of 138 individuals from 16 populations were collected, largely covering the natural distribution of R. kwangtungense. The genetic diversity within the R. kwangtungense populations was extremely low (HO = 0.048 ± 0.019; HE = 0.033 ± 0.011). Mantel tests revealed isolation-by-distance pattern (R2 = 0.38, P < 0.001), and AMOVA analysis showed that the genetic variation of R. kwangtungense occurs mainly between populations (86.88%, K = 7). Between 23 and 21 Ma, R. kwangtungense underwent a period of rapid differentiation that coincided with the rise of the Himalayas and the establishment of the East Asian monsoon. According to ENM and population demographic history, the suitable area and effective population size of R. kwangtungense decreased sharply during the glacial period and expanded after the last glacial maximum (LGM). CONCLUSION: Our study shows that the distribution pattern of southern China mountain relict flora may have developed during the panplain stage between the middle Oligocene and the early Miocene. Then, the flora later fragmented under the force of orogenesis, including intermittent uplift during the Cenozoic Himalayan orogeny and the formation of abundant rainfall associated with the East Asian monsoon. The findings emphasized the predominant role of geographical processes in shaping relict plant distribution patterns.

Palladium-Catalyzed Carbonylation Reaction of Indole/Pyrrole Involving HCFO-1233zd (E).

3-Indole-3-one is a key intermediate in the synthesis of many drugs and plays an important role in synthetic chemistry and biochemistry. A new method for synthesizing trifluoromethylated 3-indoleketones by Pd(0)-catalyzed carbonylation was introduced. In the absence of additives, 1-chloro-3,3,3-trifluoropropyl (an inexpensive and environmentally friendly synthetic block of trifluoromethyl) reacts with indole and carbon monoxide to generate trifluoromethylindole ketones with good yields, regioselectivity, and chemical selectivity; furthermore, the products exhibit strong resistance to basic functional groups, such as alkynes, aldehydes, and esters. In addition to the conversion of indole compounds into corresponding products, pyrrole and heteroindole may be suitable for corresponding chemical transformations. This study provides a synthetic method for the further construction of trifluoromethylated 3-indole ketones.

Immunogenicity evaluation of primary polio vaccination schedule with inactivated poliovirus vaccines and bivalent oral poliovirus vaccine.

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.

Dibutyl phthalate (DBP) promotes Epithelial-Mesenchymal Transition (EMT) to aggravate liver fibrosis into cirrhosis and portal hypertension (PHT) via ROS/TGF-ß1/Snail-1 signalling pathway in adult rats.

OBJECTIVE: The primary objective of this study was to investigate the toxicological impact of Dibutyl phthalate (DBP) on the process of liver fibrosis transitioning into cirrhosis and the subsequent development of portal hypertension (PHT) through the mechanism of epithelial-mesenchymal transition (EMT) mediated by the ROS/TGF-ß/Snail-1 signaling pathway. METHOD: Carbon tetrachloride (CCl4) (1 mg/kg) was introduced in adult rats by oral feeding in CCl4 and CCl4+DBP groups twice a week for 8 weeks, and twice for another 8 week in CCl4 group. DBP was introduced by oral feeding in the CCl4+DBP group twice over the following 8 weeks. We subsequently analyzed hemodynamics measurements and liver cirrhosis degree, hepatic inflammation and liver function in the different groups. EMT related genes expression in rats in the groups of Control, DBP, CCl4 and CCl4+DBP were measured by immunohistochemistry (IHC). Enzyme-linked immunosorbent Assay (ELISA), qRT-PCR, western blot were used to detect the EMT related proteins and mRNA gene expression levels in rats and primary hepatocytes (PHCs). Reactive oxygen species (ROS) were examined with a ROS detection kit. RESULTS: The results showed that the CCl4+DBP group had higher portal pressure (PP) and lower mean arterial pressure (MAP) than the other groups. Elevated collagen deposition, profibrotic factor, inflammation, EMT levels were detected in DBP and CCl4+DBP groups. ROS, TGF-ß1 and Snail-1 were highly expressed after DBP exposure in vitro. TGF-ß1 had the potential to regulate Snail-1, and both of them were subject to regulation by ROS. CONCLUSION: DBP could influence the progression of EMT through its toxicological effect by ROS/TGF-ß1/Snail-1 signalling pathway, causing cirrhosis and PHT in final. The findings of this research might contribute to a novel comprehension of the underlying toxicological mechanisms and animal model involved in the progression of cirrhosis and PHT, and potentially offered a promising therapeutic target for the treatment of the disease.

Balancing selection on an MYB transcription factor maintains the twig trichome color variation in Melastoma normale.

BACKGROUND: The factors that maintain phenotypic and genetic variation within a population have received long-term attention in evolutionary biology. Here the genetic basis and evolution of the geographically widespread variation in twig trichome color (from red to white) in a shrub Melastoma normale was investigated using Pool-seq and evolutionary analyses. RESULTS: The results show that the twig trichome coloration is under selection in different light environments and that a 6-kb region containing an R2R3 MYB transcription factor gene is the major region of divergence between the extreme red and white morphs. This gene has two highly divergent groups of alleles, one of which likely originated from introgression from another species in this genus and has risen to high frequency (> 0.6) within each of the three populations under investigation. In contrast, polymorphisms in other regions of the genome show no sign of differentiation between the two morphs, suggesting that genomic patterns of diversity have been shaped by homogenizing gene flow. Population genetics analysis reveals signals of balancing selection acting on this gene, and it is suggested that spatially varying selection is the most likely mechanism of balancing selection in this case. CONCLUSIONS: This study demonstrate that polymorphisms on a single transcription factor gene largely confer the twig trichome color variation in M. normale, while also explaining how adaptive divergence can occur and be maintained in the face of gene flow.

Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Transcriptome analysis of mesenteric arterioles changes and its mechanisms in cirrhotic rats with portal hypertension.

Portal hypertension (PHT) is a major cause of liver cirrhosis. The formation of portosystemic collateral vessels and splanchnic vasodilation contribute to the development of hyperdynamic circulation, which in turn aggravates PHT and increases the risk of complications. To investigate the changes in mesenteric arterioles in PHT, cirrhotic rat models were established by ligating the common bile ducts. After 4 weeks, the cirrhotic rats suffered from severe PHT and splanchnic hyperdynamic circulation, characterized by increased portal pressure (PP), cardiac output (CO), cardiac index (CI), and superior mesenteric artery (SMA) flow. Mesenteric arterioles in cirrhotic rats displayed remarkable vasodilation, vascular remodeling, and hypocontractility. RNA sequencing was performed based on these findings. A total of 1,637 differentially expressed genes (DEGs) were detected, with 889 up-regulated and 748 down-regulated genes. Signaling pathways related to vascular changes were enriched, including the vascular endothelial growth factor (VEGF), phosphatidylinositol-3-kinase-AKT (PI3K-AKT), and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) signaling pathway, among others. Moreover, the top ten hub genes were screened according to the degree nodes in the protein-protein interaction (PPI) network. Functional enrichment analyses indicated that the hub genes were involved in cell cycle regulation, mitosis, and cellular response to oxidative stress and nitric oxide (NO). In addition, promising candidate drugs for ameliorating PHT, such as resveratrol, were predicted based on hub genes. Taken together, our study highlighted remarkable changes in the mesenteric arterioles of cirrhotic rats with PHT. Transcriptome analyses revealed the potential molecular mechanisms of vascular changes in splanchnic hyperdynamic circulation.

Nightmare or delight: Taxonomic circumscription meets reticulate evolution in the phylogenomic era.

Phylogenetic studies in the phylogenomics era have demonstrated that reticulate evolution greatly impedes the accuracy of phylogenetic inference, and consequently can obscure taxonomic treatments. However, the systematics community lacks a broadly applicable strategy for taxonomic delimitation in groups characterized by pervasive reticulate evolution. The red-fruit genus, Stranvaesia, provides an ideal model to examine the influence of reticulation on generic circumscription, particularly where hybridization and allopolyploidy dominate the evolutionary history. In this study, we conducted phylogenomic analyses integrating data from hundreds of single-copy nuclear (SCN) genes and plastomes, and interrogated nuclear paralogs to clarify the inter/intra-generic relationship of Stranvaesia and its allies in the framework of Maleae. Analyses of phylogenomic discord and phylogenetic networks showed that allopolyploidization and introgression promoted the origin and diversification of the Stranvaesia clade, a conclusion further bolstered by cytonuclear and gene tree discordance. With a well-inferred phylogenetic backbone, we propose an updated generic delimitation of Stranvaesia and introduce a new genus, Weniomeles. This new genus is distinguished by its purple-black fruits, thorns trunk and/or branches, and a distinctive fruit core anatomy characterized by multilocular separated by a layer of sclereids and a cluster of sclereids at the top of the locules. Through this study, we highlight a broadly-applicable workflow that underscores the significance of reticulate evolution analyses in shaping taxonomic revisions from phylogenomic data.

Hemolymph Node - An Immunomorphlogical Organ: Modeling the Hemolymph Node by Allografting Renal Tissue in the Rat.

There is no authoritative characterization of the attributes of the hemolymph node (HLN) since Gibbes' first description in 1884. Early reports showed that HLN are found near the kidney in human and animals with the feature of numerous erythrocytes in sinuses. Subsequent studies mainly focused on anatomy and histology, such as the source, distribution, and quantity of erythrocytes in sinuses. Recent articles mentioned that the emergence of HLN was related to immunity, but there was no strong evidence to support this hypothesis. Therefore, it is still uncertain whether the HLN is an organ of anatomy, histology, or immunology. It has been found that the development of HLN could be elicited in the parathymic area by stimuli such as Escherichia coli, allogeneic breast cancer cells, and renal tissue that were injected/transplanted into the tail of rats in our pilot studies. In this study, the model of the HLN was established by transferring allogeneic renal tissue in the rat. Intrasinusoidal erythrocytes of the node were the component for producing a red macroscopic appearance, while macrophage-erythrocyte-lymphocyte rosettes were the major immunomorphological changes, reflecting the immune activity against the invasion of the allogeneic tissue within the node. Therefore, the HLN is an immunomorphological organ.

Functional and structural MRI based obsessive-compulsive disorder diagnosis using machine learning methods.

BACKGROUND: The success of neuroimaging in revealing neural correlates of obsessive-compulsive disorder (OCD) has raised hopes of using magnetic resonance imaging (MRI) indices to discriminate patients with OCD and the healthy. The aim of this study was to explore MRI based OCD diagnosis using machine learning methods. METHODS: Fifty patients with OCD and fifty healthy subjects were allocated into training and testing set by eight to two. Functional MRI (fMRI) indices, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DC), and structural MRI (sMRI) indices, including volume of gray matter, cortical thickness and sulcal depth, were extracted in each brain region as features. The features were reduced using least absolute shrinkage and selection operator regression on training set. Diagnosis models based on single MRI index / combined MRI indices were established on training set using support vector machine (SVM), logistic regression and random forest, and validated on testing set. RESULTS: SVM model based on combined fMRI indices, including ALFF, fALFF, ReHo and DC, achieved the optimal performance, with a cross-validation accuracy of 94%; on testing set, the area under the receiver operating characteristic curve was 0.90 and the validation accuracy was 85%. The selected features were located both within and outside the cortico-striato-thalamo-cortical (CSTC) circuit of OCD. Models based on single MRI index / combined fMRI and sMRI indices underperformed on the classification, with a largest validation accuracy of 75% from SVM model of ALFF on testing set. CONCLUSION: SVM model of combined fMRI indices has the greatest potential to discriminate patients with OCD and the healthy, suggesting a complementary effect of fMRI indices on the classification; the features were located within and outside the CSTC circuit, indicating an importance of including various brain regions in the model.

Laparoscopic total extraperitoneal (TEP) inguinal hernia repair with preperitoneal closed-suction drainage reduced postoperative complications.

BACKGROUND: Although laparoscopic total extraperitoneal (TEP) inguinal hernia repair has the advantages of less bleeding, less trauma, less pain, and fast recovery, there are several issues that need to be addressed. This study aims to evaluate the effectiveness of preperitoneal closed­suction drainage on reducing postoperative complications in TEP inguinal hernia repair. METHODS: A retrospective analysis of 122 patients who underwent TEP inguinal hernia repair between June 2018 and June 2021 was performed. The patients were divided into the drainage group and the non-drainage group according to whether the drainage tube was placed or not. Clinical data, surgical procedures and outcome of these patients were collected and analyzed to assess the effectiveness of drainage. RESULTS: A total of 122 patients undergoing TEP surgery were screened, of which 22 were excluded. Most of the patients were male with right indirect inguinal hernia. There was no difference in the mean length of hospital stay between the two groups. Postoperative pain was alleviated by preperitoneal closed­suction drainage 24 h after operation (p = 0.03). The rate of complications such as scrotal edema, seroma and urinary retention in the drainage group was significantly lower than that in the non-drainage group (p < 0.05). Multivariate regression analysis showed that drainage was beneficial to reduce postoperative complications (OR, 0.015; 95% CI, 0.002-0.140; p < 0.01). In addition, it was worth noting that in subgroup analysis, patients with hernia sac volume > 10 cm3 might receive more clinical benefits by placing drainage tube. CONCLUSION: In TEP inguinal hernia repair, placing drainage tube is a simple and feasible traditional surgical treatment, which can promote postoperative recovery without increasing the risk of infection, especially in patients with large hernia sac volume.

A Power Allocation Scheme for MIMO-NOMA and D2D Vehicular Edge Computing Based on Decentralized DRL.

In vehicular edge computing (VEC), some tasks can be processed either locally or on the mobile edge computing (MEC) server at a base station (BS) or a nearby vehicle. In fact, tasks are offloaded or not, based on the status of vehicle-to-infrastructure (V2I) and vehicle-to-vehicle (V2V) communication. In this paper, device-to-device (D2D)-based V2V communication and multiple-input multiple-output and nonorthogonal multiple access (MIMO-NOMA)-based V2I communication are considered. In actual communication scenarios, the channel conditions for MIMO-NOMA-based V2I communication are uncertain, and the task arrival is random, leading to a highly complex environment for VEC systems. To solve this problem, we propose a power allocation scheme based on decentralized deep reinforcement learning (DRL). Since the action space is continuous, we employ the deep deterministic policy gradient (DDPG) algorithm to obtain the optimal policy. Extensive experiments demonstrate that our proposed approach with DRL and DDPG outperforms existing greedy strategies in terms of power consumption and reward.

Deep Reinforcement Learning-Based Power Allocation for Minimizing Age of Information and Energy Consumption in Multi-Input Multi-Output and Non-Orthogonal Multiple Access Internet of Things Systems.

Multi-input multi-output and non-orthogonal multiple access (MIMO-NOMA) Internet-of-Things (IoT) systems can improve channel capacity and spectrum efficiency distinctly to support real-time applications. Age of information (AoI) plays a crucial role in real-time applications as it determines the timeliness of the extracted information. In MIMO-NOMA IoT systems, the base station (BS) determines the sample collection commands and allocates the transmit power for each IoT device. Each device determines whether to sample data according to the sample collection commands and adopts the allocated power to transmit the sampled data to the BS over the MIMO-NOMA channel. Afterwards, the BS employs the successive interference cancellation (SIC) technique to decode the signal of the data transmitted by each device. The sample collection commands and power allocation may affect the AoI and energy consumption of the system. Optimizing the sample collection commands and power allocation is essential for minimizing both AoI and energy consumption in MIMO-NOMA IoT systems. In this paper, we propose the optimal power allocation to achieve it based on deep reinforcement learning (DRL). Simulations have demonstrated that the optimal power allocation effectively achieves lower AoI and energy consumption compared to other algorithms. Overall, the reward is reduced by 6.44% and 11.78% compared the to GA algorithm and random algorithm, respectively.

Biomimetic Hierarchically Silver Nanowire Interwoven MXene Mesh for Flexible Transparent Electrodes and Invisible Camouflage Electronics.

Flexible transparent electrodes demand high transparency, low sheet resistance, as well as excellent mechanical flexibility simultaneously, however they still remain to be a great challenge due to"trade-off" effect. Herein, inspired by a hollow interconnected leaf vein, we developed robust transparent conductive mesh with biomimetic interwoven structure via hierarchically self-assembles silver nanowires interwoven metal carbide/nitride (MXene) sheets along directional microfibers. Strong interfacial interactions between plant fibers and conductive units facilitate hierarchically interwoven conductive mesh constructed orderly on flexible and lightweight veins while maintaining high transparency, effectively avoiding the trade-off effect between optoelectronic properties. The flexible transparent electrodes exhibit sheet resistance of 0.5 Ω sq-1 and transparency of 81.6%, with a remarkably high figure of merit of 3523. In addition, invisible camouflage sensors are further successfully developed as a proof of concept that could monitor human body motion signals in an imperceptible state. The flexible transparent conductive mesh holds great potential in high-performance wearable optoelectronics and camouflage electronics.

Mouse lung organoid responses to reduced, increased, and cyclic stretch.

Most lung development occurs in the context of cyclic stretch. Alteration of the mechanical microenvironment is a common feature of many pulmonary diseases, with congenital diaphragmatic hernia (CDH) and fetal tracheal occlusion (FETO, a therapy for CDH) being extreme examples with changes in lung structure, cell differentiation, and function. To address limitations in cell culture and in vivo mechanotransductive models, we developed two mouse lung organoid (mLO) mechanotransductive models using postnatal day 5 (PND5) mouse lung CD326-positive cells and fibroblasts subjected to increased, decreased, and cyclic strain. In the first model, mLOs were exposed to forskolin (FSK) and/or disrupted (DIS) and evaluated at 20 h. mLO cross-sectional area changed by +59%, +24%, and -68% in FSK, control, and DIS mLOs, respectively. FSK-treated organoids had twice as many proliferating cells as other organoids. In the second model, 20 h of 10.25% biaxial cyclic strain increased the mRNAs of lung mesenchymal cell lineages compared with static stretch and no stretch. Cyclic stretch increased TGF-ß and integrin-mediated signaling, with upstream analysis indicating roles for histone deacetylases, microRNAs, and long noncoding RNAs. Cyclic stretch mLOs increased αSMA-positive and αSMA-PDGFRα-double-positive cells compared with no stretch and static stretch mLOs. In this PND5 mLO mechanotransductive model, cell proliferation is increased by static stretch, and cyclic stretch induces mesenchymal gene expression changes important in postnatal lung development.

When tropical and subtropical congeners met: Multiple ancient hybridization events within Eriobotrya in the Yunnan-Guizhou Plateau, a tropical-subtropical transition area in China.

Global climate changes during the Miocene may have created ample opportunities for hybridization between members of tropical and subtropical biomes at the boundary between these zones. Yet, very few studies have explored this possibility. The Yunnan-Guizhou Plateau (YGP) in Southwest China is a biodiversity hotspot for vascular plants, located in a transitional area between the floristic regions of tropical Southeast Asia and subtropical East Asia. The genus Eriobotrya (Rosaceae) comprises both tropical and subtropical taxa, with 12 species recorded in the YGP, making it a suitable basis for testing the hypothesis of between-biome hybridization. Therefore, we surveyed the evolutionary history of Eriobotrya by examining three chloroplast regions and five nuclear genes for 817 individuals (47 populations) of 23 Eriobotrya species (including 19 populations of 12 species in the YGP), plus genome re-sequencing of 33 representative samples. We concluded that: (1) phylogenetic positions for 16 species exhibited strong cytonuclear conflicts, most probably due to ancient hybridization; (2) the YGP is a hotspot for hybridization, with 11 species showing clear evidence of chloroplast capture; and (3) Eriobotrya probably originated in tropical Asia during the Eocene. From the Miocene onwards, the intensification of the Eastern Asia monsoon and global cooling may have shifted the tropical-subtropical boundary and caused secondary contact between species, thus providing ample opportunity for hybridization and diversification of Eriobotrya, especially in the YGP. Our study highlights the significant role that paleoclimate changes probably played in driving hybridization and generating rich species diversity in climate transition zones.

Anisotropic thermal and electrical transport properties induced high thermoelectric performance in an Ir2Cl2O2 monolayer.

In recent years, the energy crisis and global warming have been urgent problems that need to be solved. As is known, thermoelectric (TE) materials can transfer heat energy to electrical energy without air pollution. High-throughput calculations as a novel approach are adopted by screening promising TE materials. In this paper, we use first-principles calculations combined with the semiclassical Boltzmann transport theory to estimate the TE performance of monolayer Ir2Cl2O2 according to the prediction that Ir2Cl2O2 has potential as a good TE material via high-throughput calculations. The low thermal conductivities of 1.73 and 4.68 W mK-1 of Ir2Cl2O2 along the x- and y-axes are calculated, respectively, which exhibits the strong anisotropy caused by the difference in group velocities of low-frequency phonon modes. Then, the electronic transport properties are explored, and the figure of merit ZT is eventually obtained. The maximum ZT value reaches 2.85 (0.40) along the x-axis (y-axis) at 700 K, revealing that the TE properties of the Ir2Cl2O2 monolayer are highly anisotropic. This work reveals that the anisotropic layer Ir2Cl2O2 exhibits high TE performance, which confirms that it is feasible to screen excellent TE materials via high-throughput calculations.

Knockdown of MAGE-A6 enhanced the irradiation sensitivity of non-small cell lung cancer cells by activating the AMPK pathway.

Non-small cell lung cancer is a common respiratory tumor. The mortality rate of lung cancer patients has continued to rise in recent years. Several studies revealed that the expression of melanoma antigen 6 (MAGE-A6) promoted the development of multiple types of cancer. In addition, the suppression of AMPK pathway could restrict the radiosensitization of prostate cancer cells. Inhibition of MAGE-A6 activated the AMPK pathway in colorectal cancer cells. However, whether the MAGE-A6 could regulate the radiosensitivity of non-small cell lung cancer cells by regulating of the AMPK pathway is unclear. In this study, we established the MAGE-A6 knockdown in A549 and H1299 cells. Next, the apoptosis and proliferation of these cells were detected by the flow cytometry analysis and colony formation assay after the irradiation, respectively. Then, the expression of p-AMPKα1 and p-S6K1 in these cells was explored by the western blotting. After that, we inhibited the expression of AMPKα1 in MAGE-A6 knockdown cells. The proliferation and apoptosis of these cells were detected with colony formation assay and flow cytometry analysis. Finally, the tumor formation of these cells was detected in nude mice. Our results showed that inhibition of MAGE-A6 suppressed the proliferation and aggravated the apoptosis of A549 and H1299 cells after the irradiation. Knockdown of MAGE-A6 activated the expression of p-AMPKα1 and repressed the expression of p-S6K1 in these cells. Suppression of AMPKα1 in MAGE-A6 knockdown cells abolished these effects. Knockdown of MAGE-A6 also enhanced the radiosensitivity of these cells in vivo. These results suggested that inhibition of MAGE-A6 promoted the radiosensitivity of non-small cell lung cancer cells by activating AMPK pathway. Therefore, MAGE-6 has the potential to be explored as the therapeutic target for the treatment of non-small cell lung cancer in clinical.