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CD147 is involved in various physiological processes and plays important roles for tumor metastasis. Glycosylation of the protein determines numerous functions of CD147. Up to now, hardly any sensor has been developed for detecting glycosylation of CD147 in live cells. There is a pressing requirement of development of a selective and continuous biosensor for cell imaging. The emergence of gene-encoded fluorescence resonance energy transfer (FRET) sensor provides a new way to develop the sensors to analysts. We designed and constructed novel gene-encoded FRET proteins sensing glycosylation of CD147 by measuring FRET ratio of two intermolecular motifs. With the decrease of CD147 glycosylation level in cells, the FRET ratio increased significantly. The specificity of the sensor targeting to CD147 was also determined by siRNA interference experiment. Finally, continuous living cell image of deglycosylation process of CD147 using the newly developed sensor has been performed successfully. The work not only provides useful tools for analyzing glycosylation of CD147 in living cells, but also implicates alternative strategy for detecting other glycosylated proteins.

Introduction High-altitude cerebral edema (HACE) is considered to be the end-stage of acute mountain sickness (AMS); however, its pathophysiological mechanism remains unknown. Increasing evidences support that inflammation is an important risk factor for the occurrence of HACE. Including our published papers, previous studies demonstrated that the levels of IL-6, IL-1β, and TNF-α in both serum and hippocampus were increased in the mouse HACE model induced by LPS stimulation combined with hypobaric hypoxia exposure; however, the expression profile of other cytokines and chemokines remains unknown. Objective This study was to analyze the expression profile of cytokines and chemokines in the HACE model. Methods The mouse HACE model was established by LPS stimulation combined with hypobaric hypoxia exposure (LH). The mice were divided into the normoxic group, LH-6 h group, LH-1 d group, and LH-7 d group. Brain water content (BWC) was determined using the wet/dry weight ratio. The levels of 30 cytokines and chemokines in the serum and hippocampal tissue were detected using LiquiChip. The mRNA expression of cytokines and chemokines in hippocampal tissue were determined by q-PCR. Results In the current study, we found that the brain water content was increased after the combinational treatment of LPS and hypobaric hypoxia. The results of LiquiChip showed that, in the serum and hippocampal tissue, most factors in all 30 cytokines and chemokines were dramatically upregulated at 6 h, and then declined at the 1st d and 7th d. Among these factors, G-CSF, M-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β were all increased in both serum and hippocampal tissue at 6 h. In addition, the results of q-PCR showed the mRNA levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in hippocampal tissue were dramatically upregulated at 6 h. Conclusion This study showed that the dynamic expression profile of 30 cytokines and chemokines in a mouse HACE model induced by LPS plus hypobaric hypoxia. The levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in both serum and hippocampus were significantly increased at 6 h, which may be involved in the occurrence and development of HACE.

Because calcined alpha alumina (α-Al2O3) inherits the morphology characteristic of milled precursors, it is expected that the α-Al2O3 morphology could be improved by controlling the precursor morphology through the use of different milling processes. The microstructure evolution of the boehmite precursor under different milling treatments (planetary ball milling [PBM] and high-energy ball milling [HEBM]) and its influence on the microstructure of as-synthesized α-Al2O3 were investigated. The experimental results indicate that HEBM has a stronger modification effect in crystallinity, particle size and dispersibility of the boehmite precursor than PBM, which is of great importance to inhibit the formation of the typical worm-like structure of α-Al2O3. The microstructure of α-Al2O3 was further improved by the introduction of NH4BF4, NH4F and NH4Cl as additives. In particular, polygon-like α-Al2O3 particles with a size of 0.5 μm and a good dispersibility were prepared by calcination of the precursor with 30 h of HEBM and 20 wt.% NH4BF4.

Here we present a novel peptide-based fluorescent "turn-on" molecule P1 for detecting RNA, in a double or single strand, AU-rich or CG-rich. Both computational and experimental studies indicate that the detection efficiency depends on the binding affinity of P1 and conformational changes. P1 could be applied for cell imaging without any additional transfection vectors. Selective detection of RNA in cells was determined by RNase digestion. Successful application of P1 for RNA imaging in cell mitosis reveals that it may have broad applications in research, biotechnology and medical science.

Understanding plant thermal tolerance is fundamental to predicting impacts of extreme temperature events that are increasing in frequency and intensity across the globe. Extremes, not averages, drive species evolution, determine survival and increase crop performance. To better prioritize agricultural and natural systems research, it is crucial to evaluate how researchers are assessing the capacity of plants to tolerate extreme events. We conducted a systematic review to determine how plant thermal tolerance research is distributed across wild and domesticated plants, growth forms and biomes, and to identify crucial knowledge gaps. Our review shows that most thermal tolerance research examines cold tolerance of cultivated species; c. 5% of articles consider both heat and cold tolerance. Plants of extreme environments are understudied, and techniques widely applied in cultivated systems are largely unused in natural systems. Lastly, we find that lack of standardized methods and metrics compromises the potential for mechanistic insight. Our review provides an entry point for those new to the methods used in plant thermal tolerance research and bridges often disparate ecological and agricultural perspectives for the more experienced. We present a considered agenda of thermal tolerance research priorities to stimulate efficient, reliable and repeatable research across the spectrum of plant thermal tolerance.

Herein, nano-sized α-Al2O3 powders were successfully synthesized at low temperatures via unidirectional ball milling of Al(OH)3 and addition of an AlF3 additive. The effects of the rotational direction in planetary ball milling on the α-phase transformation and morphology of α-Al2O3 were studied. Unidirectional rotation was observed to be significantly more helpful than bidirectional rotation with regard to improving the α-phase transformation and microstructure of α-Al2O3. Further, α-Al2O3 was obtained at a lower temperature (800 °C) by employing unidirectional ball milling; this was because gibbsite agglomerates (20–100 μm) could be refined into micro-sized curled flocs with a high specific surface area (124.95 m2 ∙ g−1) by performing unidirectional ball milling for 9 h. The addition of 1 wt% AlF3 accelerated the gas-phase mass transfer, which could effectively promote α-phase transformation and decrease the temperature at which α-Al2O3 was obtained. In comparison with the pyramidal α-Al2O3 polyhedron that exhibited a size range of 0.2–2 μm, homogeneous α-Al2O3 polyhedron with the size of approximately 100 nm was prepared at the temperature range of 910–940 °C via unidirectional ball milling.

Zhang, Guangbo, Yanzhao Zhou, Zhengtao Cao, Xiang Cheng, Xiangpei Yue, Tong Zhao, Ming Zhao, Yongqi Zhao, Ming Fan, and Lingling Zhu. Preliminary intermittent hypoxia training alleviates the damage of sustained normobaric hypoxia on human hematological indexes and cerebral white matter.

Preeclampsia (PE), the most significant adverse exposure to cardiovascular risk during pregnancy, is one of the three major factors contributing to maternal and fetal mortality and the leading cause of preterm birth. Recently, various miRNAs have been reported to participate in PE occurrence and development. Nevertheless, the regulatory impact of miR-195-5p in PE is still indistinct.Quantitative realtime-PCR (qRT-PCR), western blot, and fluorescence in situ hybridization (FISH) assay were performed to examine miR-195-5p and FGF2 expressions in PE serum samples or HTR-8/SVneo and TEV-1 cells. CCK8, flow cytometry, wound scratch, and transwell assays were conducted to determine cell viability, cycle, apoptosis, migration, and invasion. Dual-luciferase reporter assay unveiled the relationship between miR-195-5p and FGF2. Migration-related and invasion-related protein expressions were measured by western blot assay.miR-195-5p was prominently downregulated while FGF2 was increased in serum samples from PE patients and hypoxia-treated human trophoblast cells. FGF2 was predicted as a downstream target of miR-195-5p and targeted association was verified by dual-luciferase reporter assay. Functional experiments elaborated that miR-195-5p could facilitate trophoblast cell proliferation and metastasis but hinder cell cycle and apoptosis. Inversely, overexpressing of FGF2 could reverse the effects of miR-195-5p on trophoblast cell growth.miR-195-5p was decreased in PE serum samples and cell lines, serving as a potential biomarker in protecting PE exacerbation by targeting FGF2.

Colorectal cancer (CRC) is the third most common malignant tumor in the world and the second leading cause of cancer-related deaths, with the liver as the most common site of distant metastasis. The prognosis of CRC with liver metastasis is poor, and most patients cannot undergo surgery. In addition, conventional antitumor approaches such as chemotherapy, radiotherapy, targeted therapy, and surgery result in unsatisfactory outcomes. In recent years, immunotherapy has shown good prospects in the treatment of assorted tumors by enhancing the host's antitumor immune function, and it may become a new effective treatment for liver metastasis of CRC. However, challenges remain in applying immunotherapy to CRC with liver metastasis. This review examines how the microenvironment and immunosuppressive landscape of the liver favor tumor progression. It also highlights the latest research advances in immunotherapy for colorectal liver metastasis and identifies immunotherapy as a treatment regimen with a promising future in clinical applications.

In the present work, the effects of the pre-firing temperature of andalusite aggregates (5–3 mm) on the conversion of andalusite as well as the volume stability and oxidation resistance of the Al2O3–SiC–C castables were investigated. The phases of the andalusite aggregates were tested via X-ray diffraction, and their microstructures as well as those of the castables were characterized via scanning electron microscopy. The linear expansion of the castables decreased with increase in the pre-firing temperature of andalusite, as less residual andalusite in the pre-fired aggregates lowered its transformation in the castables during firing at high temperatures. Moreover, the higher amounts of SiO2-rich glass produced by andalusite pre-fired at high temperatures and secondary mullite generated between andalusite and the matrixes were both favorable to the production of castables with denser structure. This prevented the diffusion of O2 into the castables and improved their oxidation resistance.

Remote ischemic conditioning (RIC) confers protection on major organs from hypoxic/ischemic injuries; however, its impacts on attention network function and blood oxygen levels in unacclimatized adults exposed to high altitudes have yet to be elucidated. In this study, we recruited 120 healthy male volunteers, of which one was exposed to high altitude and the other was exposed to low altitude. The two cohorts were further divided into RIC and sham control groups. The attentional network test (ANT) was performed to evaluate cognitive function before and after RIC treatment. Other outcomes such as heart rate, blood pressure, blood oxygen saturation, cerebral tissue oxygenation index (CTOI), and cerebrovascular hemodynamic indices were also evaluated. Prior to RIC treatment, there were no significant differences in orienting or executive function between the treatment and control arms of either cohort. Alerting function was significantly lower in the high-altitude cohort than in the low-altitude cohort. There were significant reductions in both blood oxygen and CTOI in the high-altitude cohort relative to the low-altitude cohort, while the pulse index (PI) of the former cohort was significantly increased. After RIC treatment, there was a significant difference in alerting function between the high-altitude RIC group and its associated control. The CTOI of the treatment group increased from 60.39±3.40% to 62.78±4.40%, and blood oxygenation also improved. Furthermore, this group showed a significant reduction in its PI. Exposure to high-altitude environments had a significant impact on alerting function, blood oxygen, CTOI, and PI. RIC ameliorated changes in attentional function, as well as blood oxygen and CTOI, suggesting that it potentially alters cerebrovascular compliance upon exposure to high altitude.

As water-soluble calcium chloride (CaCl2) could be uniformly distributed in the castable compared with commercial CAC particles (25–55 μm), the effect of CaCl2 addition (0–2 wt%) on the distribution of CA6 and the properties of the alumina-based castables (especially thermal shock resistance and permanent linear change) after calcination at 1450 °C were investigated. It was found that the alumina-based castable with 1.5 wt% CaCl2 had the minimum PLC value of 0.18% and the maximum value of residual CMOR ratio (25%). The castable matrix fired at 800–1450 °C was examined by XRD to identify the phase evolution of castable with the addition of CaCl2. The 1450 °C fired castable matrix without and with 1.5 wt% CaCl2 additive was analyzed by SEM to determine the morphology evolution of CA6. The improved volume stability and enhanced thermal-shock resistance of the alumina-based castables containing CaCl2 additive has been illustrated through the formation of CA6 with smaller size and more uniform distribution.

In this study, the CAR-like multivalent aptamer nanoparticles (X-polymers) were assembled with the dimer of murine CD28 RNA aptamer (CD28Apt7), the tetramer of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) RNA aptamer (Del60), and a folic acid labeled ssDNA fragment in a stable nucleic acid three-way junction scaffold (3WJ). Results showed that the X-polymers could recognize both the mCD28 and mCTLA-4 molecules. Confocal imaging and flow cytometry assays showed that the X-polymers could target both T cells and B16 cells in vitro. With the first costimulatory signals provided by the CD3 antibodies, the X-polymers could increase T cell proliferation and reverse the inhibitory effect of interleukin-2 (IL-2) secreting caused by exogenous B7.1 molecules on T cells in vitro. Results of our study also showed that X-polymers could inhibit mouse melanoma B16 cell growth both in vitro and in vivo. Our study demonstrated for the first time that the multivalent aptamer nanoparticle-activated T cells could fulfill the function of CAR-T, which promised a novel approach to developing a multi-functional design of aptamer drugs with potential CAR-like characteristics to enhance the safety of CAR-T cell immunotherapy., Graphical Abstract, Shao and colleagues assembled multivalent aptamer nanoparticles with potential CAR-like characteristics. The CAR-like nanoparticles could activate T cells and inhibit melanoma growth both in vitro and in vivo. They put forward a concept of CAR-like aptamer drugs that may avoid the complexity of CAR-T preparation of exogenous transduction.

Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Chronic inflammation is recognized as a key causal factor in the development and progression of DN, and the imbalance of M1/M2 macrophages (Mφ) contributes to this process. Mesenchymal stem cells (MSCs) have been reported to prevent renal injuries via immune regulation in diabetic models, but whether these benefits are owing to the regulation of Mφ, and the underlying signaling pathways are unknown. Here, we showed that MSCs elicited Mφ into M2 phenotype and prevented renal injuries in DN mice, but these effects were abolished when the Mφ were depleted by clodronate liposomes (Lipo-Clod), suggesting that Mφ were necessary for renal protection of MSCs in DN mice. Moreover, the MSCs promoted M2 polarization was attributable to the activation of transcription factor EB (TFEB) and subsequent restore of lysosomal function and autophagy activity in Mφ. Furthermore, in vivo adoptive transfer of Mφin vivo (Mφ from DN + MSCs mice) or MφMSCs (Mφ cocultured with MSCs in vitro) to DN mice improved renal function. While, TFEB knockdown in Mφ significantly abolished the protective role of MφMSCs. Altogether, these findings revealed that MSCs suppress inflammatory response and alleviate renal injuries in DN mice via TFEB-dependent Mφ switch.

Aims: Cisplatin, an anticancer drug, always leads to nephrotoxicity by causing mitochondrial dysfunction. As a major mechanism for cellular self-degradation, autophagy has been proven to protect against cisplatin-induced acute kidney injury (AKI). Based on the activation of autophagy induced by trehalose, we aimed to investigate the nephroprotective effects of trehalose on cisplatin-induced AKI and its underlying mechanisms. Results: Due to the activation of autophagy, mitochondrial dysfunction (mitochondrial fragmentation, depolarization, reactive oxygen species (ROS), and reduced ATP generation) and apoptosis induced by cisplatin were markedly inhibited in trehalose-treated HK2 cells in vitro. Based on the transcriptional regulation role of transcription factor EB (TFEB) in autophagy and lysosome, we characterized trehalose-induced nuclear translocation of TFEB. Furthermore, consistent with trehalose treatment, overexpression of TFEB inhibited cell injury induced by cisplatin. However, the protective effects of trehalose were largely abrogated in tfeb-knockdown cells. In vivo, cisplatin injection resulted in severe kidney dysfunction and histological damage in mice. Trehalose administration activated TFEB-mediated autophagy, alleviated mitochondrial dysfunction and kidney injury in AKI mice. Innovation and conclusion: Our data suggest that trehalose treatment preserves mitochondria function via activation of TFEB-mediated autophagy and attenuates cisplatin-induced kidney injury.

To investigate the relationship between the nutrition status of infants with bronchopulmonary dysplasia (BPD) at the first 4 weeks of life and the likelihood of developing neonatal malnutrition.A total of 1064 infants were divided into a BPD group and a non-BPD group. After propensity score matching, there were 282 infants in each group. Infants were further divided into a neonatal malnutrition （NM） group and a well-nourished （WN） group. Clinical factors, nutrition intake, and growth parameters were collected and analyzed. Multivariate logistic regression model was used to determine the factors associated with neonatal malnutrition.1. Compared with infants in the non-BPD group, the infants in BPD group had more fluid intake and lower calorie and protein intake after the second week, longer invasive ventilation time, and longer time to total oral feeding and parenteral nutrition (PN), and the difference was more significant in NM infants than in WN infants (P0.05). 2. The weight/length, body mass index, triponderal mass index, and weight gain velocity in the BPD group were significantly lower than in the non-BPD group (P0.05) and lower in NM infants than in WN ones (P0.05). 3. Multivariable system regression analysis showed that invasive ventilation time, lipid intake in week 4, time to reach full feeding, and duration of PN were independent risk factors for NM.Enhancing calorie and macronutrient intake, reducing invasive ventilation, and achieving full gastrointestinal feeding early may be effective measures to avoid malnutrition in infants with BPD.

This paper is devoted to the practical tracking control for a class of flexible-joint robotic manipulators driven by DC motors. Different from the related literature where control constraint is neglected and the disturbances are excluded or only exist in one subsystem, actuator saturation is considered in this paper while the disturbances are present in all the three subsystems. This leads to the incapability of the traditional schemes on this topic. For this, a novel control design scheme is proposed by skillfully incorporating adaptive dynamic compensation technique, constructive methods of command filters and an auxiliary system for the actuator saturation into the backstepping framework, and in turn to design a practical tracking controller which ensures that all the states of the resulting closed-loop system are bounded and the system output practically tracks the reference signal. It is worthwhile strengthening that a more wider class of reference signals can be tracked since they are only first order continuously differentiable but twice or more in the related literature. Finally, a numerical example is provided to validate the effectiveness of the proposed theoretical results.

We investigated the role of the STING1-CXCR3 axis using database data and verified it in a mouse model bearing Lewis lung carcinoma (LLC) cells exposed to hydrogen peroxide (H

Gynostemma pentaphyllum possesses neuroprotective bioactivity. However, the effect of gypenosides on hypoxia-induced neural damage remains obscure. In this study, Gyp, the active fraction extracted from G. pentaphyllum and its bioactive compounds as well as the underlying molecular mechanisms were investigated. Eighteen dammarane-type saponins were isolated from Gyp. The absolute configurations of six unreported compounds (13-18) were assessed via electron capture detection (ECD) analyses. The results of cell viability assay showed that Gyp and its bioactive compounds (13-16 and 18) effectively protected PC12 cells from hypoxia injury. Gyp pretreatment also improved mice spatial memory impairment caused by hypoxia exposure. At the molecular level, Gyp and its bioactive compounds could activate the signaling pathways of ERK, Akt, and CREB in vitro and in vivo. In summary, Gyp and its bioactive compounds could prevent hypoxia-induced injury via ERK, Akt, and CREB signaling pathways.

Aims: Clinical use of cisplatin (Cisp), one of the most widely used, common, and effective chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Previous studies suggest that hydrogen sulfide (H2S) alleviates Cisp-induced acute kidney injury (AKI). However, the underlying mechanism remains largely unclear. Results: A single intraperitoneal injection of Cisp is employed to induce AKI, and the mice exhibit severe kidney dysfunction and histological damage at day 4 after Cisp injection. Here, we reported that H2S alleviated Cisp-caused renal toxicity via SIRT3 activation and subsequent improvement of mitochondrial ATP production. Using a biotin-switch assay, we showed that H2S increased S-sulfhydration of SIRT3 and induced deacetylation of its target proteins (OPA1, ATP synthase β, and superoxide dismutase 2). These effects of H2S were associated with a reduction of mitochondrial fragmentation, an increase in ATP generation, and less oxidative injury. Notably, the S-sulfhydration of SIRT3 induced by H2S was abrogated when Cys256, Cys259, Cys280, and Cys283 residues on SIRT3 (two zinc finger domains) were mutated. Innovation and Conclusion: Our data suggest that H2S attenuates Cisp-induced AKI by preventing mitochondrial dysfunction via SIRT3 sulfhydrylation. Antioxid. Redox Signal. 31, 1302-1319.

Gastric cancer (GC) is a common malignant tumor, and patients with GC have a low survival rate due to limited effective treatment methods. Angiogenesis and immune evasion are two key processes in GC progression, and they act synergistically to promote tumor progression. Tumor vascular normalization has been shown to improve the efficacy of cancer immunotherapy, which in turn may be improved through enhanced immune stimulation. Therefore, it may be interesting to identify synergies between immunomodulatory agents and anti-angiogenic therapies in GC. This strategy aims to normalize the tumor microenvironment through the action of the anti-vascular endothelial growth factor while stimulating the immune response through immunotherapy and prolonging the survival of GC patients.

Neuroinflammation caused by peripheral lipopolysaccharides (LPS) under hypoxia is a key contributor to the development of high altitude cerebral edema (HACE). Our previous studies have shown that gypenosides and their bioactive compounds prevent hypoxia-induced neural injuries in vitro and in vivo. However, their effect on neuroinflammation-related HACE remains to be illustrated. The present study aimed to investigate the effects of GP-14 in HACE mouse model.HACE mice were treated with GP-14 (100 and 200 mg/kg) for 7 days. After the treatments, the level of serum inflammation cytokines and the transcription of inflammatory factors in brain tissue were determined. The activation of microglia, astrocyte and the changes of IgG leakage and the protein levels of tight junction proteins were detected. Furthermore, the inflammatory factors and nuclear factor-κB (NF-κB) signaling pathway in BV-2 cells and primary microglia were detected.GP-14 pretreatment alleviated both the serum and neural inflammatory responses caused by LPS stimulation combined with hypobaric hypoxia exposure. In addition, GP-14 pretreatment inhibited microglial activation, accompanied by a decrease in the M1 phenotype and an increase in the M2 phenotype. Moreover, the disruption of the blood brain barrier (BBB) integrity, including increased IgG leakage and decreased expression of tight junction proteins, was attenuated by GP-14 pretreatment. Based on the BV-2 and primary microglial models, the inflammatory response and activation of the NF-κB signaling pathway were also inhibited by GP-14 pretreatment.Taken together, our results demonstrated that GP-14 exhibited prominent protective roles against neuroinflammation and BBB disruption in a mouse HACE model. GP-14 could be a potential choice for the treatment of HACE in the future.

Water is an important medium for virus transmission and viral pathogens are increasingly appreciated as a significant water safety issue. However, the effect of pipe biofilms on viral pathogens remains unclear. This research aimed to investigate the dissemination of viruses in a full-scale drinking water supply system (DWSS) and the effect of pipe biofilms on viral pathogens in bulking water. Viral pathogens, pathogenic viral hosts, and viral virulence factors (VFs) were found to disseminate from source water to tap water. The proportion of virus and viral VFs in the biofilm was far less than that in water. The contribution of biofilms in pipe wall to viruses and viral VFs in bulking water was less than 4%, and viruses in the biofilm had no obvious effect on pathogenic viruses in water. Dominant viruses carrying VFs changed from Cyanobacteria virus to Mycobacterium virus after advanced water treatment. Mycobacterium and organics were identified as the key factors influencing composition and abundance of viral VFs, which could explain 41.1% of the variation in viral virulence in the water supply system. Host bacteria and organics may be used as the key targets to control the risk of viruses in DWSSs.

To study changes in the intestinal flora associated with inflammatory bowel disease (IBD) in the Han population of southwest China, 48 participants were enrolled, 18 of whom had been diagnosed with IBD. Stool samples were collected from the participants. Sequencing of 16S rRNA gene was used to measure and identify the components of the intestinal flora. Diversity analysis and multivariate statistical analysis were conducted to study differences in intestinal flora between patients with IBD and healthy controls. The goods coverage, observed species, Shannon, and Simpson indices of alpha diversity were different (The online version contains supplementary material available at 10.1007/s12088-022-01014-z.

Although drought and high temperature are two main factors affecting crop productivity and forest vegetation dynamics in many areas worldwide, little work has been done to describe the effects of heat combined with pre-existing drought on photochemical function in diverse plant species. This study investigated the biophysical status of photosystem II (PSII) and its dynamic responses under 2-day heat stress during a 2-week drought by measuring the polyphasic chlorophyll fluorescence rise (OJIP) kinetics. This study examined four contrasting species: a C3 crop/grass (wheat), a C4 crop/grass (sorghum), a temperate tree species (Fraxinus chinensis) and a tropical tree species (Radermachera sinica). Principal component analysis showed that the combination of heat and drought deviated from the effect of heat or drought alone. For all four species, a linear mixed-effects model analysis of variance of the OJIP parameters showed that the deviation arose from decreased quantum yield and increased heat dissipation of PSII. The results confirmed, in four contrasting plant species, that heat stress, when combined with pre-existing drought, exacerbated the effects on PSII photochemistry. These findings provide direction to future research and applications of chlorophyll fluorescence rise OJIP kinetics in agriculture and forestry, for facing increasingly more severe intensity and duration of both heat and drought events under climate change.

BackgroundPrimary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare type of non-small cell lung cancer (NSCLC). Currently, anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) has become an important treatment for NSCLC. Anti-human PD-1 monoclonal antibodies, such as nivolumab, significantly prolong the survival time of patients with advanced lung adenocarcinoma and lung squamous cell carcinoma. However, there are few reports on the therapeutic effect, drug resistance mechanism, and strategies to overcome resistance to anti-PD-1/PD-L1 treatment in advanced pulmonary LELC. We report the case of a patient with advanced pulmonary LELC harboring fibroblast growth factor receptor (FGFR)3 gene amplification that showed resistance to nivolumab. After treatment with anlotinib, a multi-targeted small-molecule tyrosine kinase inhibitor, the patient’s resistance to nivolumab was reversed. She achieved long-term disease remission with a combination of anlotinib and nivolumab treatment.Case PresentationA 68-year-old woman was diagnosed with stage IVA pulmonary LELC. After multiple-line chemotherapy, her disease progressed. Since the PD-L1 expression rate of the patient was 90%, nivolumab was administered. However, the therapeutic effect of nivolumab was not ideal; the disease continued to progress, and a new cervical lymph node metastasis appeared. FGFR3 gene amplification was detected in lymph node metastasis. Based on this gene abnormality, we added anlotinib to the treatment. After two cycles of anlotinib and nivolumab, the metastatic focus of the patient was significantly reduced. The patient continued to receive this combined treatment and achieved remission for more than 15 months.ConclusionPulmonary LELC with FGFR3 gene amplification may not respond well to nivolumab monotherapy. The combination of anlotinib and nivolumab can reverse the resistance to nivolumab in pulmonary LELC with FGFR3 gene amplification.

Supplementation with estradiol (E2) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E2 levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage embryo transfers, E2 levels on progesterone initiation day were significantly lower in the ongoing pregnancy/live birth (OP/LB) group than in the non-OP/LB group (214.75 ± 173.47 vs. 253.20 ± 203.30 pg/ml; P = 0.023). In addition, there were downward trends in implantation, clinical pregnancy and OP/LB rates with increasing E2 levels. However, in blastocyst-stage embryo transfers, such trends were not observed, and E2 levels were not significant difference between the OP/LB group and the non-OP/LB group (201.66 ± 182.14 vs. 197.89 ± 212.83 pg/ml; P = 0.884). The results suggests that elevated progesterone-initiation-day E2 levels may negatively affect pregnancy outcomes during artificial cleavage-stage embryo transfers. However, it is not necessary to monitor E2 levels when transferring blastocysts in artificial FET cycles.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever, and the causative pathogen, the SFTS virus (SFTSV), was first discovered in China in 2010. In this study, a retrospective analysis of 86 patients that diagnosed with SFTS from two five-year periods (2011-2015 and 2016-2020) that was performed to explore the changes in epidemiology, clinical characteristics, laboratory parameters and prognosis between those two periods. The results showed that there were significant differences in age, the proportion of farmers, geographical distribution, the incidence of multiple organ dysfunction, the decrease in thrombocyte count, and the elevations of serum AST and lipase levels between the two groups (p

Energy is now seen as a significant resource that develops abundant on the world economy, with short supply and development. A study found that renewable energy systems are needed to prevent shortages. Hence, all the focus in this study to decrease electricity consumption and reduce the overall completion times for a regular console in green technology networks was an efficient and scalable production genomic solution. A Renewable green energy resources smart city (RGER-SC) framework is proposed that used a multi-target evolutionary algorithm was hybridized to be effective and calculated arithmetically in this study. This work deals with fostering renewable energy incorporation by adjusting federal charges to increase the energy accounting practitioners. Besides, this report analyses the timely generation of delay-tolerant demands and the maintenance of district heating at network infrastructure. In comparison, capacity differentials between consumers and information centres are considered and evaluated using the Renewable green energy resources smart city (RGER-SC) framework for energy conservation and controlled task management at an industrial level.

Background Alzheimer’s disease (AD) is a progressive, degenerative, and terminal disease without cure. There is an urgent need for a new strategy to treat AD. The aim of this study was to investigate the effects of intermittent hypoxic treatment (IHT) on cognitive functions in a mouse model of AD and unravel the mechanism of action of IHT. Methods Six-month-old APPswe/PS1dE9 (APP/PS1) male mice were exposed to hypoxic environment (14.3% O2) 4 h/day for 14 days or 28 days. Cognitive functions were measured by Morris water maze test after either 14 days or 42 days of interval. Thereafter the distribution of amyloid plaque and microglial activation were determined by mouse brain immunohistochemistry, while the amyloid beta (Aβ) and inflammatory cytokines were measured by ELISA and Western Blot. Microarray was used for studying gene expressions in the hippocampus. Results IHT for 14 days or 28 days significantly improved the spatial memory ability of the 6-month-old APP/PS1 mice. The memory improvement by 14 days IHT lasted to 14 days, but not to 42 days. The level of Aβ plaques and neurofilament accumulations was reduced markedly after the IHT exposure. IHT reduced the pro-inflammatory cytokines IL-1β, IL-6 levels, and β-secretase cleavage of APP processing which implies reduced Aβ production. Microarray analysis revealed a large number of genes in the hippocampus were significantly altered which are known to be metabolism-regulated genes. Conclusions This study provides evidence of the beneficial effect of IHT on the progression of AD by alleviating memory impairment, reducing Aβ accumulation and inflammation in the brain. IHT can be developed as a novel measure to relieve the progression of AD by targeting multiple pathways in the AD pathogenesis.

In recent years, the tail zone of the largest tributary of the largest freshwater lake, Poyang Lake in China, has been challenged by serious water scarcity caused by the drop of the water level during dry season. It is difficult to establish effective remedial measures because of the lack of research regarding the causes of the water level drop. Therefore, this phenomenon and its causes were analyzed in this study. First, a series of daily discharge and water level data from six hydrological and water level stations that has been recorded since the 1950s was used to determine the historical trends in the dry water level using the Mann–Kendall test. Based on the combination of topographic data of typical cross section and classic water conservancy equations, the causes of the water level decrease were studied. The results show that the water level drop in this region was not notable until 2003. Subsequently, continuous deterioration became noticeable. Influenced by various factors, the cumulative water level drop in the dry season reached 4.06 m. This demonstrates the weak correlation between the water level drop and inflow. Instead, the water level decrease was mainly affected by the riverbed undercutting and slightly influenced by changes of the water level in the four lower branches. Effective alleviation strategies should include the strict limitation of the incision of the riverbed and increase in the downstream water level.

Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjogren's syndrome (SS). The present study aimed to investigate the role of miR-155-5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon-γ (IFN-γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription-quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual-luciferase reporter assay was performed to verify the interaction between miR-155-5p and arrestin β2 (ARRB2). The protein levels in the NF-κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treatment with IFN-γ increased miR-155-5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR-155-5p promoted IFN-γ-induced apoptosis and inflammation in SGECs. Overexpression of miR-155-5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin-6 and tumor necrosis factor-α, and decreased Bcl-2 protein expression in IFN-γ-treated SGECs. By contrast, all of the effects aforementioned were reversed following miR-155-5p knockdown. These results demonstrated that miR-155-5p activated the NF-κB signaling pathway, where treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR-155-5p overexpression on the inflammatory factors in IFN-γ-induced SGECs. miR-155-5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR-155-5p overexpression on the inflammatory response, apoptosis and the NF-κB signaling pathway in IFN-γ-treated SGECs. Collectively, results from the present study suggest that miR-155-5p may activate the NF-κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR-155-5p may serve to be a potential target for the treatment of SS.

Stroke is a leading cause of long-term disability worldwide; survivors often show sensorimotor and cognitive deficits. Therapeutic exercise is the most common treatment strategy for rehabilitating patients with stroke via augmentation of neurogenesis, angiogenesis, neurotrophic factors expression, and synaptogenesis. Neurogenesis plays important roles in sensorimotor and cognitive functional recovery, and can be promoted by exercise; however, the mechanism underlying this phenomenon remains unclear. In this study, we explored the effects of treadmill exercise on sensorimotor and cognitive functional recovery, as well as the potential molecular mechanisms underlying the promotion of neurogenesis in a rat model of transient middle cerebral artery occlusion (tMCAO). We found that treadmill exercise facilitated sensorimotor and cognitive functional recovery after tMCAO, and that neural stem/progenitor cell proliferation, differentiation, and migration were enhanced in the ipsilateral subventricular and subgranular zones after tMCAO. Meanwhile, the newborn neurons induced by treadmill exercise after tMCAO had the similar function with pre-existing neurons. Treadmill exercise significantly increased CD200 and CD200 receptor (CD200R) levels in the ipsilateral hippocampus and cortex. Further study revealed that treadmill exercise-induced neurogenesis and functional recovery were clearly inhibited, while Il-β and Tnf-α expression were upregulated, following lentivirus (LV)-induced suppression of post-stroke CD200R expression. Consistent with the effect of treadmill exercise, CD200Fc (a CD200R agonist) markedly promoted neurogenesis and functional recovery after stroke. In addition, CD200Fc could further enhance the functional recovery induced by treadmill exercise after stroke. Our results demonstrate the beneficial role of treadmill exercise in promoting neurogenesis and functional recovery via activating the CD200/CD200R signaling pathway and improving the inflammatory environment after stroke. Thus, the CD200/CD200R signaling pathway is a potential therapeutic target for functional recovery after stroke.

The R2R3-MYB transcription factor FOUR LIPS (FLP) controls the stomatal terminal division through transcriptional repression of the cell cycle genes CYCLIN-DEPENDENT KINASE (CDK) B1s (CDKB1s), CDKA; 1, and CYCLIN A2s (CYCA2s). We mutagenized the weak mutant allele flp-1 seeds with ethylmethane sulfonate and screened out a flp-1 suppressor 1 (fsp1) that suppressed the flp-1 stomatal cluster phenotype. FSP1 encodes RPA2a subunit of Replication Protein A (RPA) complexes that play important roles in DNA replication, recombination, and repair. Here, we show that FSP1/RPA2a functions together with CDKB1s and CYCA2s in restricting stomatal precursor proliferation, ensuring the stomatal terminal division and maintaining a normal guard-cell size and DNA content. Furthermore, we provide direct evidence for the existence of an evolutionarily conserved, but plant-specific, CDK-mediated RPA regulatory pathway. Serine-11 and Serine-21 at the N terminus of RPA2a are CDK phosphorylation target residues. The expression of the phosphorylation-mimic variant RPA2a(S11,21/D) partially complemented the defective cell division and DNA damage hypersensitivity in cdkb1;1 1;2 mutants. Thus, our study provides a mechanistic understanding of the CDK-mediated phosphorylation of RPA in the precise control of cell cycle and DNA repair in plants.

Hexagonal α-Al2O3 platelets with about 1-μm diameter and 0.2-μm thickness are prepared by the calcination of a milled Al(OH)3 precursor with NH4F and NH4Cl additives. The influences of the ball milling treatment and the composite additive on the microstructure of α-Al2O3 micro-powders are studied. The results indicate that the particle size distribution of α-Al2O3 is highly dependent on the aggregate size of the Al(OH)3 precursor and that the morphology of α-Al2O3 can be significantly favored by the addition of 5 wt.% NH4F and 5 wt.% NH4Cl as additives. The growth velocity of the (0001) plane is significantly reduced because of the accelerated growth rate of other crystal faces caused by the increase of gas phase mass transfer. The combined effect of composite additives and precursor ball milling treatment leads to the generation of well-developed α-Al2O3 platelets with uniform size distribution.

A new pectin (ALP-2) was extracted from the roots of Arctium lappa L. with the molecular weight of 1.84 × 106 Da. ALP-2 was composed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, xylose and arabinose. Results of NMR revealed that the dominant linkage types of ALP-2 were →4-α-GalpA-6-OMe-(1→, →2-α-Rha-(1→, →5-α-Araf-(1→ and →3,6-β-Galp-(1→. The ELISA results indicated ALP-2 was a typical pectin with HG chain and RG-I chain. The rheological experiments showed that ALP-2 fluid exhibited shear thinning behavior. The viscosity of ALP-2 was mainly affected by concentration, temperature, and pH. The ALP-2 fluid with elastic properties at high frequencies could be used as a thickener in the food industry. Moreover, ALP-2 with the dosages of 200 mg/kg and 400 mg/kg exhibited strong anti-constipation activity in vivo. ALP-2 treated groups could improve small intestinal movement rate and increase the weight of feces significantly in constipation mice. Therefore, ALP-2 could be considered as the active component for functional food or therapeutic agent in constipation therapy.

The distribution of in situ CA6 depends on the amount of the residual calcium aluminate cement (CAC) anhydrous phase and the distribution of CAC hydrates in CAC-bonded alumina-based castables and can influence the properties (especially the volume stability) of the castables. Because the CAC hydration process is strongly related to the curing temperature, CAC-bonded alumina-based castables were cured at 5 °C, 10 °C, 25 °C, 40 °C, and 50 °C to investigate the influence of curing temperature on the volume stability of CAC-bonded alumina-based castables. The castables after curing, drying, and firing were examined by SEM to determine the distribution of the residual CAC anhydrous phase and CA6 grains. Phase compositions of the castable matrixes after drying at 110 °C and firing at 1450–1600 °C were analyzed by X-ray diffraction to identify the hydration degree and generation of CA6. The contribution of curing temperature to the volumetric stability of the castables is discussed in terms of hydration products after curing and CA6 distribution in the castables after firing at 1600 °C.

The change in demoulding strength of colloidal silica-bonded castables with and without magnesia is investigated with emphasis on the relationship between the demoulding strength and chemical bond changes. It was confirmed that the demoulding strength was raised with the presence of magnesia in colloidal silica-bonded castables because of the increased chemical bonding between the sol particles. The X-ray photoelectron spectroscopy (XPS) and the Fourier transformation infrared spectroscopy (FTIR) results indicate the formation of new Si–O–Mg chemical bond from the decreased O 1s and Si 2p binding energy, and the appearance of weak vibration peaks at 668 and 419 cm−1 in the spectrum of colloidal silica with the addition of MgO after curing at 30°C for 24 hours. The reaction between colloidal silica and magnesia could promote the formation of –Si–O–Mg–O–Si–bonds, which is the primary reason for the demoulding strength improvement.

There are about 66 tributaries distributed in the Three Gorges Reservoir (TGR) area. As obvious deposition has been observed at estuary of most tributaries estuary since the water-impoundment of TGR, the possibility of sedimentation leading to form entrance bar at estuary of tributaries should be highly concerned. Based on data of topography and cross-sections, the DEM digital elevation model is established to calculate the aggradation volume at the estuary of tributaries in TGR, also the scouring and silting thickness at estuary will be demonstrated. Changes of cross-sections and thalweg caused by aggradation are also studied. The results show that: (1) The aggradation volume at estuary of 66 tributaries in TGR was 180 million m3 from March 2003 to November 2011; (2) hydrodynamic conditions at estuary of tributaries weakened after the operation of TGR, which is the root cause of sediment deposition. The extent of sediment silting was affected by sediment from the tributaries and backward water from the mainstream, meanwhile the dynamic state of river course at estuary had an important influence on the range of aggradation; (3) sediment deposited at the estuary mainly derived from backward water of mainstream, and less from the tributaries. As sediment concentrations both in mainstream and tributaries decreased obviously and will be continually maintain a low level, there is little risk for the formation of entrance bar of tributaries in TGR.

To assess the feasibility of potassium aluminosilicates (KAlSiO4, KAS2 and KAlSi2O6, KAS4) as the refractory sagger material for the calcination of Li-ion battery cathode materials, the interaction behavior between KAS2 (KAS4) and the Li(NixCoyMnz)O2 (LNCM) material was investigated at temperatures ranging from 800 to 1100 °C. The phase composition and microstructure of calcined KAS2 (KAS4)-LNCM precursor mixtures were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The results indicate that potassium aluminosilicates exhibit superior resistance to corrosion by LNCM materials compared with mullite and MgO-based refractories, and rarely react with LNCM materials during calcination.

The distribution and size of in-situ CA6 is related to CAC particle size in CAC-bonded corundum-based castables and would influence the properties of the castables. In order to investigate the influence of CAC particle size on the properties of CAC-bonded castables, CAC was milled for 2 h to reduce particle sizes. The properties of CAC-bonded castables with different CAC particle sizes were investigated in terms of demoulding strength after curing at 30 °C, drying strength after drying at 110 °C and, in particular, volumetric stability and thermal shock resistance after firing at 1450 °C, respectively. The results indicate the volumetric stability and thermal shock resistance of the CAC-bonded castables were improved by replacing unground CAC (D50 = 12.39 μm) with ground CAC (D50 = 1.36 μm) because the incorporation of ground CAC produced smaller-sized CA6 with more uniform distribution after firing at 1450 °C.

NB-3, a member of the contactin/F3 subgroup in the immunoglobulin superfamily, plays an important role in neural development and injury recovery. The blood brain barrier (BBB) is typically involved in the pathophysiology of neural disorders, such as hypoxic-ischemic brain injury. Our previous research found that NB-3 protects against brain damage in a mouse stroke model. However, its role in high-altitude disorders caused by hypobaric hypoxia exposure remains unknown. In the present study, we found that NB-3 was expressed in brain microvascular endothelial cells (BMECs) and responded to hypoxia stimulation. Conditional knockout of NB-3 in endothelial cells increased BBB leakage and downregulated tight junction proteins in vivo. NB-3 deficiency promoted the downregulation of tight junction proteins under Lipopolysaccharide (LPS)/hypoxia stimulation. Conversely, overexpression or supplementation with NB-3 alleviated endothelial barrier injuries. Transcriptome sequencing showed that NB-3 regulated various cell attachment genomic changes, including the Notch signaling pathway. Blocking the Notch signaling pathway increased VEGF/VEGFR2 pathway activation induced by LPS/hypoxia. Collectively, we present evidence that NB-3 plays key roles in maintaining BBB integrity under high-altitude cerebral edema conditions.