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Background and purpose: Long non-coding RNA (lncRNA) LINC01410, with a length of 647 bp, participates in a variety of tumor biological processes. However, the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma (ESCC) remain unclear. This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion, to provide a potential prognostic indicator and therapeutic target for individuals with ESCC. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas (TCGA). Gene Set Enrichment Analysis (GSEA) was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC. A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected. This project has been approved by the Hospital Ethics Committee (First Affiliated Hospital of Xinxiang Medical College, No. 2018036; First People's Hospital of Pingdingshan City, No. 2019-018). The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410. Stable transfected cells (EC109/NC, EC109/OE, EC9706/NC and EC9706/KD) were selected in primary cell culture medium containing puromycin. The expression of LINC01410 was detected by RTFQ-PCR. The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay. T cell factor/lymphoid enhancer factor 1 (TCF/LEF1) luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway. The expressions of Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signal pathway related proteins in ESCC cells were detected by Western blot. Results: By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2, we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues (P

Abstract We examined the joint association of physical activity (PA) and socio-economic status (SES) on all-causes and cardiovascular disease (CVD) mortality in 6945 elderly Koreans (mean age: 71.6 years, 41.8% male) using data from the Korean National Health and Nutrition Examination Survey (2007–2013) and death data from Statistics Korea (2019). The SES included household income and education level. PA was assessed using the IPAQ and categorized according to the 2018 PA Guidelines. In stratified analyses using Cox proportional hazards by SES adherence to PA guidelines those who low household income group was associated with a reduced risk of all-cause mortality and CVD mortality, while in the lowest educational level group, it was associated with a reduced risk of all-cause mortality and CVD mortality. In the joint analysis, PA was associated with a significant reduction in all-cause mortality in all groups when compared with those who did not meet PA those who had the lowest SES. However, PA with CVD mortality risk was not significantly associated in the ‘upper-middle’ income and ‘high school’ education groups. The study revealed that PA significantly association mortality, particularly among older adults with low SES. This finding suggests the potential for targeted government interventions to promote healthy aging.

The amphibian skin secretions are excellent sources of bioactive peptides, some of which and their derivatives exhibit multiple properties, including antibacterial and antagonism against bradykinin. A novel peptide Senegalin-2 was isolated from the skin secretions of Kassina senegalensis frog. Senegalin-2 relaxed rat bladder smooth muscle (EC50 17.94 nM) and ileum smooth muscle (EC50 135 nM), inhibited S. aureus and MRSA at 2 μM, and exhibited low hemolytic activity with no cytotoxicity. To design effective bradykinin antagonists, Senegalin-2 was conjugated with bradykinin to synthesize Senegalin-2BK. This modification retained potent activity against Gram-positive bacteria. Compared to Senegalin-2, Senegalin-2BK significantly reduced hemolysis and exhibited a more than threefold increase in the selectivity index. Furthermore, Senegalin-2BK contracted the bladder (EC50 2.83 μM) and ileum (EC50 56.64 nM)’s smooth muscle. The pretreatment with 10−7 M Senegalin-2BK reduced the 10−6 M bradykinin contraction on the bladder by over 70%. In conclusion, Senegalin-2 has dual functionalities as an antibacterial agent and muscle relaxant, positioning it as a potential therapeutic candidate for managing overactive bladder. As a synthetically derived bradykinin antagonist and myotropic peptide with antibacterial properties, Senegalin-2BK shows promise in effective therapies for relieving pain, inflammation, and addressing muscular disorders such as urinary retention, constipation, and infections.

Amyotrophic lateral sclerosis (ALS), commonly known as motor neuron disease, is a neurodegenerative disorder characterized by the progressive degeneration of both upper and lower motor neurons. This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients’ quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.

Background The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S228P mutation IgG4 as the structural basis to avoid the activation of immune cells or complement. However, little attention has been paid to the Fc–Fc interactions between IgG4 and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative to avoid the undesirable Fc–Fc interactions and Fc receptor binding derived effects observed with IgG4. This study provides a comprehensive evaluation of anti-PD-1 mAbs of these two frameworks.Methods Trastuzumab and rituximab (both IgG1), wildtype IgG1 and IgG4 were immobilized on nitrocellulose membranes, coated to microplates and biosensor chips, and bound to tumor cells as targets for Fc–Fc interactions. Wildtype IgG1 and IgG4, anti-PD-1 mAb nivolumab (IgG4 S228P), penpulimab (Fc-null IgG1), and tislelizumab (Fc-null IgG4 S228P-R409K) were assessed for their binding reactions to the immobilized IgG proteins and quantitative kinetic data were obtained. To evaluate the effects of the two anti-PD-1 mAbs on immune responses mediated by trastuzumab and rituximab in the context of combination therapy, we employed classic immune models for antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement dependent cytotoxicity. Tumor-bearing mouse models, both wildtype and humanized, were used for in vivo investigation. Furthermore, we also examined the effects of IgG1 and IgG4 on diverse immune cell populationsResults Experiments demonstrated that wildtype IgG4 and nivolumab bound to immobilized IgG through Fc–Fc interactions, diminishing antibody-dependent cell-mediated cytotoxicity and phagocytosis reactions. Quantitative analysis of kinetic parameters suggests that nivolumab and wildtype IgG4 exhibit comparable binding affinities to immobilized IgG1 in both non-denatured and denatured states. IgG4 exerted inhibitory effects on various immune cell types. Wildtype IgG4 and nivolumab both promoted tumor growth in wildtype mouse models. Conversely, wildtype IgG1, penpulimab, and tislelizumab did not show similar adverse effects.Conclusions Fc-null IgG1 represents a safer choice for anti-PD-1 immunotherapies by avoiding both the adverse Fc–Fc interactions and Fc-related immune inhibitory effects of IgG4. Fc-null IgG4 S228P-R409K and Fc-null IgG1 displayed similar structural properties and benefits. This study contributes to the understanding of immunotherapy resistance and the advancement of safer immune therapies for cancer.

Abstract Background Using grip strength as a predictor of nutritional risk and early ambulation for gastrointestinal tumor surgery and determining its critical value have not been reported. This study was designed to explore the influencing factors of early postoperative ambulation ability for patients with gastrointestinal tumors who underwent laparoscopic surgery. Methods Four-hundred twenty-seven patients with gastrointestinal tumors who underwent laparoscopic surgery at three tertiary A hospitals in Beijing were prospectively enrolled. Subsequently, logistic regression analysis was conducted to determine the independent predictors of early postoperative ambulation. Logistic regression analyses for the different gender were also performed. In addition, the effectiveness of preoperative grip strength measurement in nutritional risk assessment was analyzed by using nutritional risk score 2002 (NRS 2002) as a control. Results The included cases were comprised of 283 male and 144 female patients, with an age of 59.35 ± 11.70 years. Gender, preoperative grip strength, operative time, and number of indwelling tubes were independent predictors of early postoperative ambulation. In the male group, lower preoperative grip strength and more indwelling tubes were independent risk factors for early postoperative ambulation. In the female group, lower preoperative grip strength and extended operating time were independent risk factors. Moreover, preoperative grip strength (male

Due to the lack of drilling data in the Zhu 1 Depression of the Pear River Mouth Basin, the Enping 17 Sag is taken as an example in this paper to solve the problem of comprehensive identification of underground distribution of high-quality source rocks. Based on the analysis of the geological background, sedimentary characteristics and petrophysical characteristics of source rocks, seismic inversion is guided by the constraints of the petrophysical characteristics of the source rocks in different sedimentary environments. According to the statistics of the relationship between the lithofacies of drilled source rocks and the inversion resistance, a semi-quantitative prediction of the spatial distribution of favorable source rocks is made by geological modeling, and the rationality of prediction method and results is analyzed in combination with the recognition of the geochemical origin type and source of crude oil, to discuss the geological and geophysical identification method of the underground distribution of high-quality source rocks with lack of drilling data. The more reductive the depositional environment of source rocks in the Paleogene Wenchang Formation, the lower the impedance value of high-quality source rocks, and the greater the impedance difference between poor source rocks or non-source rocks. The third, fourth and fifth members of Wenchang Formation are the main source rocks of the Enping 17 Sag, which can be supported by the study of crude oil biomarkers. In the small sags of the Pearl River Mouth Basin with basically clear petroleum geological background conditions, establishing the quantitative and semi-quantitative relationship between the lithofacies of source rocks and the inversion impedance value is helpful to quickly clarify the development interval and scale of main source rocks. This method has a good prospect of popularization and application.

Calcite veins are widely developed in organic-rich shale, and their petrological characteristics and genetic mechanism are the focus of research. The Electron Back Scatter Diffraction (EBSD) can characterize the micro-structure and orientation of mineral crystals in situ, which has been widely used in the field of material science and has been rapidly developed in the field of geology. In order to clarify the crystal characte-ristics of fibrous calcite veins in organic-rich shale of the Longmaxi Formation in the Sichuan Basin, EBSD was used to characterize the mineralogical and crystallographic characteristics of calcite veins. The calcite veins are mainly composed of calcite and quartz. Calcite is the main body, with an average grain size of 372 μm, while quartz is mainly distributed at the interface of calcite lamina. The calcite crystals in calcite veins belong to trigonal[JP] or rhombohedral system, and the corresponding unit cell is trigonal or rhombohedral. The lattice parameters are a0=b0=4.99 Å, c0=17.061 Å, α=β=90°, γ=120°, respectively. Calcite veins have a certain preferred orientation on longitudinal section, which is due to the development of polysynthetic twin crystals in calcite grains. The adjacent twin crystal stripes have different crystal orientations, and the crystal misorientation is 75° while the alternate twin stripes have the same crystal orientation, and the crystal orientation of the same twin stripe is the same. In calcite grains, perfect cleavage occurs in groups with sharp angle with twin crystal stripes. Both cleavage and twin crystal stripes are formed by tectonic compression and shearing during the crystallization of calcite, and the maximum principal stress direction is parallel to the twin crystal stripes.

Background: We recently reported a novel IgG4-centered immune evasion mechanism in cancer, and this was achieved mostly through the Fc-Fc reaction of increased IgG4 to cancer-bound IgG in cancer microenvironment. The mechanism was suggested to be related to cancer hyperprogressive disease (HPD) which is a side-effect often associated to IgG4 subtype PD-1 antibody immunotherapy. HPD was reported to occur in cancers with certain mutated genes including KRAS and such mutations are often associated to glutathione (GSH) synthesis. Therefore, we hypothesize that IgG4 and GSH may play a synergistic role in local immunosuppression of cancer. Methods: Quantitatively analyzed the distribution and abundance of GSH and IgG4 in human cancer samples with ELISA and immunohistochemistry. The interactions between GSH and IgG4 were examined with Electrophoresis and Western Blot. The synergistic effects of the two on classic immune responses were investigated in vitro. The combined effects were also tested in a lung cancer model and a skin graft model in mice. Results: We detected significant increases of both GSH and IgG4 in the microenvironment of lung cancer, esophageal cancer, and colon cancer tissues. GSH disrupted the disulfide bond of IgG4 heavy chain and enhanced IgG4’s ability of Fc-Fc reaction to immobilized IgG subtypes. Combined administration of IgG4 and GSH augmented the inhibitory effect of IgG4 on the classic ADCC, ADCP, and CDC reactions. Local administration of IgG4/GSH achieved the most obvious effect of accelerating cancer growth in the mouse lung cancer model. The same combination prolonged the survival of skin grafts between two different strains of mouse. In both models, immune cells and several cytokines were found to shift to the state of immune tolerance. Conclusion: Combined application of GSH and IgG4 can promote tumor growth and protect skin graft. The mechanism may be achieved through the effect of the Fc-Fc reaction between IgG4 and other tissue-bound IgG subtypes resulting in local immunosuppression. This reaction was facilitated by increased GSH to dissociate the two heavy chains of IgG4 Fc fragment at its disulfide bonds. Our findings unveiled the interaction between the redox system and the immune systems in cancer microenvironment. It offers a sensible explanation for HPD and provides new possibilities for manipulating this mechanism for cancer immunotherapy.

Background and aimsInternet gaming disorder (IGD) and aggression (AG) are widespread phenomena around the world. Numerous studies have explored the relationship between the two but findings from such studies are inconsistent. The meta-analysis aimed to evaluate the relationship between IGD and AG as well as identify the variables moderating the relationship.MethodStudies investigating the relationship between IGD and AG were searched using selected terms to identify studies published from 1999 to 2022 on CNKI, Wanfang Data, Chongqing VIP Information Co., Ltd. (VIP), Baidu scholar, ProQuest dissertations, Taylor & Francis, Springer, Web of Science, Google Scholar, Elsevier Science (Science Direct), EBSCO, and PsycINFO. The identified studies were pooled and analyzed.ResultsA total of 30 samples comprising 20,790 subjects were identified. Results showed that there was a moderate relationship between IGD and AG (r = 0.300, 95%CI [0.246, 0.353]). Moderator analysis revealed that the relationship between IGD and AG was moderated by the region, age, and survey year.ConclusionThis meta-analysis indicated that people with a higher level of IGD might show more aggression, and people with more aggression might have a higher level of IGD. The correlation coefficient between IGD and AG was significantly higher in Asia than in Europe, higher in primary school than in middle school and university, and higher by increasing year. Overall, our findings provide a basis for developing prevention and intervention strategies against IGD and AG.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375267, 42022375267.

Diseases of the pulmonary alveolus, such as pulmonary fibrosis, are leading causes of morbidity and mortality, but exceedingly few drugs are developed for them. A major reason for this gap is that after inhalation, drugs are quickly whisked away from alveoli due to their high perfusion. To solve this problem, the mechanisms by which nano‐scale drug carriers dramatically improve lung pharmacokinetics using an inhalable liposome formulation containing nintedanib, an antifibrotic for pulmonary fibrosis, are studied. Direct instillation of liposomes in murine lung increases nintedanib's total lung delivery over time by 8000‐fold and lung half life by tenfold, compared to oral nintedanib. Counterintuitively, it is shown that pulmonary surfactant neither lyses nor aggregates the liposomes. Instead, each lung compartment (alveolar fluid, alveolar leukocytes, and parenchyma) elutes liposomes over 24 h, likely serving as “drug depots.” After deposition in the surfactant layer, liposomes are transferred over 3–6 h to alveolar leukocytes (which take up a surprisingly minor 1–5% of total lung dose instilled) in a nonsaturable fashion. Further, all cell layers of the lung parenchyma take up liposomes. These and other mechanisms elucidated here should guide engineering of future inhaled nanomedicine for alveolar diseases.

Recent reports indicate that immune cells in solid cancers have significant predictive and therapeutic value. IgG4 is a subclass of IgG and we recently found that it exerted an inhibitory effect in tumor immunity. We aimed to assess the significance of IgG4 and T cell subtypes in tumor prognosis. We investigated the density, distribution and relationship of five immune markers CD4, CD8, Foxp3, IL-10 and IgG4 with multiple immunostaining method in 118 esophageal squamous cell carcinoma (ESCC) together with clinical data. The relationship among different immune cell types and with clinical data were analyzed with Kaplan-Meier survival analysis and Cox proportional hazards model to identify independent risk factors among immune and clinicopathological parameters. Five-year survival rate of these patients treated with surgery reached 61%. Higher number of CD4+ plus CD8+ T cells predicted better prognosis (p=0.01) in tertiary lymphoid structure (TLS) and could add to the value of TNM staging. Density of the newly identified immune inhibitor IgG4+ B lymphocytes was found positively correlated to that of CD4+ cells (p=0.02) and IL-10+ cells (p=0.0005), but number of infiltrating IgG4+ cells by itself was not an independent factor for prognosis. However, increased serum concentration of IgG4 indicated a poor prognosis of ESCC (p=0.03). 5-year survival rate of esophageal cancer after surgery has been significantly improved. Increased T cells in TLS predicted better survival, suggesting that T cells in TLS may actively participate in anti-tumor immunity. Serum IgG4 could be a useful predictor of prognosis.

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.

Abstract Vertical ferroelectricity where a net dipole moment appears as a result of in-plane ionic displacements has gained enormous attention following its discovery in transition metal dichalcogenides. Based on first-principles calculations, we report on the evidence of robust vertical ferroelectricity upon interlayer sliding in layered semiconducting β-ZrI2, a sister material of polar semimetals MoTe2 and WTe2. The microscopic origin of ferroelectricity in ZrI2 is attributed to asymmetric shifts of electronic charges within a trilayer, revealing a subtle interplay of rigid sliding displacements and charge redistribution down to ultrathin thicknesses. We further investigate the variety of ferroelectric domain boundaries and predict a stable charged domain wall with a quasi-two-dimensional electron gas and a high built-in electric field that can increase electron mobility and electromechanical response in multifunctional devices. Semiconducting behaviour and a small switching barrier of ZrI2 hold promise for various ferroelectric applications, and our results provide important insights for further development of slidetronics ferroelectricity.

By combining thermal simulation experiments with core data, thin sections, scanning electron microscopy (SEM), source rock, and high-pressure mercury and gas adsorption analysis, this paper evaluates the properties and models of shale reservoirs in the upper fourth member and the lower third member of the Shahejie Formation in Dongying Sag and Zhanhua Sag. The results show that the oil shale is a high-quality source rock with petroleum generation potential. Inorganic mineral pores, organic pores, and fractures have developed with petroleum storage capacity. Clay and organic-rich soft shale lithofacies are interbedded with carbonate-rich hard shale lithofacies to form sandwich-type source–reservoir–caprock assemblages with internal sealing properties. Bitumen occurs mostly in the free state, and to a lesser extent is adsorbed, and shows flow characteristics. The migration resistance of the bitumen is displacement pressure, including capillary force and adsorption resistance, and the main force is pore fluid pressure. The migration modes of the bitumen include both subcritical flow and instantaneous flow, which are controlled by pore fluid pressure, displacement pressure, and the rock’s fracture strength. Owing to the multi-scale characteristics of the shale reservoir space, a vein-type model of a multi-scale progressive transport network is developed that obeys Murray’s law with a dominant migration pathway in the shale reservoir. The shale oil reservoir is a special lithologic reservoir controlled by the sedimentary environment and has self-generation, self-storage, and self-sealing characteristics with developed pore fluid overpressure and a multi-scale transport network.

Abstract Background The increase in atmospheric CO2 is causing a number of changes in plant growth such as increases in leaf area and number, branching, plant size and biomass, and growth rate. Despite the importance of stomatal responses to CO2, little is known about the genetic and molecular mechanisms that mediate stomatal development and movement in response to CO2 levels. Deciphering the mechanisms that sense changes in CO2 and/or HCO3 − concentration is critical for unraveling the role of CO2 in stomatal development movement. In Arabidopsis, CO2-induced stomatal closure is strongly Ca2+-dependent. To further dissect this signaling pathway and identify new components in the CO2 response pathway, we recorded [Ca2+]cyt changes in mutagenized Arabidopsis leaves and screened for mutants with abnormal guard cell behavior in response to CO2/HCO3 −. Results We observed that 1 mM HCO3 − induces [Ca2+]cys transient changes in guard cells and stomatal closure both in light and darkness. The changes in [Ca2+]cys induced by HCO3 − could be detected by an aequorin-based calcium imaging system. Using this system, we identified a number of Arabidopsis mutants defective in both [Ca2+]cyt changes and the stomatal response to CO2/HCO3 −. Conclusions We provide a sensitive method for isolating stomatal CO2/HCO3 − response genes that function early in stomatal closure and that have a role in regulating [Ca2+]cyt. This method will be helpful in elucidating the Ca2+-dependent regulation of guard cell behavior in response to CO2/HCO3 −.

Although the potential of lake facies shale oil and gas resources is enormous, the lithology is complex, heterogeneous, and obviously controlled by a sedimentary environment. By integrating cores, thin sections, X-ray diffraction analysis, trace elements, organic geochemical indexes, and paleontological data, this work studies sedimentary environment elements and sedimentary model of shale in the E1f2 member, Gaoyou Depression, Subei Basin. The shale in the E1f2 member is completely shore lacustrine deposits forming into the hot dry climate of tropical central and south Asia. The lake basin extended continuously, with brackish water, strong reduction, and medium water stratification. The transgression resulted in the rapid rise of water, salinity, reducibility, and water stratification. As the climate becomes wetter, the E1f2 water level, salinity, reduction, and stratification decrease. The shale in E1f2 members is characterized by sedimentary zones, which are divided into muddy water desalination deposit in the flooded zone, clear water salinization deposit in the transition zone, and still water salinization deposited in the clear water zone. Under palaeotopography settings of E1f2 members, combining characteristics of vertical stratification and the plane zone of the lake, an integrated sedimentary model of lacustrine shale in a flat platform has been established under climate and transgression control. The plane area of the lake could be divided into the slow slope zone, sub-depression zone, processes zone, deep slope zone, and deep depression zone, corresponding roughly to the sedimentary zones of the flooded zone, transition zone, and clear water zone. Moreover, the oil shale enriched in low-lying parts of the paleotopography is mainly deposited at the end of muddy water areas and clear water areas.

We prove that the Fubini-Study currents associated to a sequence of singular Hermitian holomorphic line bundles on a compact normal Moishezon space distribute asymptotically as the curvature currents of their metrics. [ABSTRACT FROM AUTHOR]

High levels of ammonium (NH4+) in soils inhibit plant growth and nitrogen utilization efficiency. Elucidating the underlying mechanisms of NH4+ toxicity is essential for alleviating the growth inhibition caused by high NH4+. Our previous work showed that [Ca2+]cyt-associated protein kinase 1 (CAP1) regulates root hair growth in response to NH4+ in Arabidopsis thaliana, and the cap1-1 mutant produces short root hairs under NH4+ stress conditions. However, it is unclear whether CAP1 functions in other physiological processes in response to NH4+. In the present study, we found that CAP1 also plays a role in attenuating NH4+ toxicity to promote shoot growth. The cap1-1 mutant produced smaller shoots with smaller epidermal cells compared with the wild type in response to NH4+ stress. Disruption of CAP1 enhanced the NH4+-mediated inhibition of the expression of cell enlargement-related genes. The cap1-1 mutant showed elevated reactive oxygen species (ROS) levels under NH4+ stress, as well as increased expression of respiratory burst oxidase homologue genes and decreased expression of catalase genes compared with the wild type. Our data reveal that CAP1 attenuates NH4+-induced shoot growth inhibition by promoting cell wall extensibility and ROS homeostasis, thereby highlighting the role of CAP1 in the NH4+ signal transduction pathway.

Chronic alcohol exposure can cause myocardial degenerative diseases, manifested as cardiac insufficiency, arrhythmia, etc. These are defined as alcoholic cardiomyopathy (ACM). Alcohol-mediated myocardial injury has previously been studied through metabolomics, and it has been proved to be involved in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway concerning unsaturated fatty acids biosynthesis and oxidative phosphorylation, which tentatively explored the mechanism of ACM induced by chronic drinking. To further study alcohol-induced myocardial injury, myocardial specimens from a previously successfully established mouse model of ACM were subjected to histological, echocardiographic, and proteomic analyses, and validated by real-time quantitative polymerase chain reaction (qPCR). Results of histopathology and echocardiography showed the hypertrophy of cardiomyocytes, the dilation of ventricles, and decreased cardiac function. Proteomic results, available via ProteomeXchange with identifier PXD032949, revealed 56 differentially expressed proteins (DEPs) were identified, which have the potential to be involved in the KEGG pathway related to fatty acid biosynthesis disorders, lipid metabolism disorders, oxidative stress, and, ultimately, in the development of dilated cardiomyopathy (DCM). The present study further elucidates the underlying effects of myocardial injury due to chronic alcohol intake, laying a foundation for further studies to clarify the potential mechanisms of ACM.

Plant virus vectors are ideal tools for delivery of genetic cargo into host cells for functional genomics studies and protein overexpression. Although a vast number of plant virus vectors have been developed for different purposes, the utility of a particular virus vector is generally limited. Here, we report a multipurpose plant rhabdovirus-based vector system suitable for a wide range of applications in Nicotiana benthamiana. We engineered sonchus yellow net rhabdovirus (SYNV)-based gene silencing vectors through expressing a sense, antisense, or double-stranded RNAs of target genes. Robust target gene silencing was also achieved with an SYNV vector expressing a designed artificial microRNA. In addition, ectopic expression of a short tandem target mimic RNA using the SYNV vector led to a significant depletion of the target miR165/166 and caused abnormal leaf development. More importantly, SYNV was able to harbor two expression cassettes that permitted simultaneous RNA silencing and overexpression of large reporter gene. This dual capacity vector also enabled systemic expression of a whole-molecule monoclonal antibody consisting of light and heavy chains. These results highlight the utility of the SYNV vector system in gene function studies and agricultural biotechnology and provide a technical template for developing similar vectors of other economically important plant rhabdoviruses.

Plant guard cell is essential for photosynthesis and transpiration. The aperture of stomata is sensitive to various environment factors. Carbon dioxide (CO2) is an important regulator of stomatal movement, and its signaling includes the perception, transduction and gene expression. The intersections with many other signal transduction pathways make the regulation of CO2 more complex. High levels of CO2 trigger stomata closure, and reactive oxygen species (ROS) as the key component has been demonstrated function in this regulation. Additional research is required to understand the underlying molecular mechanisms, especially for the detailed signal factors related with ROS in this response. This review focuses on Arabidopsis stomatal closure induced by high-level CO2, and summarizes current knowledge of the role of ROS involved in this process.

Generation of recombinant negative-stranded RNA viruses (NSVs) from plasmids involves in vivo reconstitution of biologically active nucleocapsids and faces a unique antisense problem where the negative-sense viral genomic RNAs can hybridize to viral messenger RNAs. To overcome this problem, a positive-sense RNA approach has been devised through expression of viral antigenomic (ag)RNA and core proteins for assembly of antigenomic nucleocapsids. Although this detour strategy works for many NSVs, the process is still inefficient. Using Sonchus yellow net rhabdovirus (SYNV) as a model; here, we develop a negative-sense genomic RNA-based approach that increased rescue efficiency by two orders of magnitude compared to the conventional agRNA approach. The system relied on suppression of double-stranded RNA induced antiviral responses by co-expression of plant viruses-encoded RNA silencing suppressors or animal viruses-encoded double-stranded RNA antagonists. With the improved approach, we were able to recover a highly attenuated SYNV mutant with a deletion in the matrix protein gene which otherwise could not be rescued via the agRNA approach. Reverse genetics analyses of the generated mutant virus provided insights into SYNV virion assembly and morphogenesis. This approach may potentially be applicable to other NSVs of plants or animals.

Serum starvation is a routine protocol for synchronizing nuclear donor cells to G0/G1 phase during somatic cell nuclear transfer (SCNT). However, abrupt serum deprivation can cause serious stress to the cells cultured in vitro, which might result in endoplasmic reticulum (ER) stress, chromosome damage, and finally reduce the success rate of SCNT. In the present study, the effects of tauroursodeoxycholic acid (TUDCA), an effective ER stress-relieving drug, on the nuclear donor cells under serum deprivation condition as well as following SCNT procedures were first assessed in the bovine. The results showed that TUDCA significantly reduced ER stress and cell apoptosis in those nuclear donor cells. Moreover, it significantly decreased the expression of Hdac1 and Dnmt1, and increased the level of H3K9 acetylation in nuclear donor cells compared with control group. SCNT reconstructed embryos cloned from TUDCA-treated donor cells showed significantly higher fusion, cleavage, blastocyst formation rate, total cell number in day 7 blastocysts, and lower apoptotic index than that from control group. In addition, the expression of Hdac1, Dnmt1 and Bax was significantly lower in blastocysts derived from TUDCA-treated donor cells than that from control group. In conclusion, TUDCA significantly reduced the ER stress of nuclear donor cells under serum starvation condition, and significantly improved the developmental competence of following SCNT reconstructed embryos when these TUDCA-treated cells were used as the nuclear donors.