Understanding vegetation phenology responses to easily ignored climate factors in china's mid-high latitudes.

Previous studies have primarily focused on the influence of temperature and precipitation on phenology. It is unclear if the easily ignored climate factors with drivers of vegetation growth can effect on vegetation phenology. In this research, we conducted an analysis of the start (SOS) and end (EOS) of the growing seasons in the northern region of China above 30°N from 1982 to 2014, focusing on two-season vegetation phenology. We examined the response of vegetation phenology of different vegetation types to preseason climatic factors, including relative humidity (RH), shortwave radiation (SR), maximum temperature (Tmax), and minimum temperature (Tmin). Our findings reveal that the optimal preseason influencing vegetation phenology length fell within the range of 0-60 days in most areas. Specifically, SOS exhibited a significant negative correlation with Tmax and Tmin in 44.15% and 42.25% of the areas, respectively, while EOS displayed a significant negative correlation with SR in 49.03% of the areas. Additionally, we identified that RH emerged as the dominant climatic factor influencing the phenology of savanna (SA), whereas temperature strongly controlled the SOS of deciduous needleleaf forest (DNF) and deciduous broadleaf forest (DBF). Meanwhile, the EOS of DNF was primarily influenced by Tmax. In conclusion, this study provides valuable insights into how various vegetation types adapt to climate change, offering a scientific basis for implementing effective vegetation adaptation measures.

A spatiotemporal atlas of cholestatic injury and repair in mice.

Cholestatic liver injuries, characterized by regional damage around the bile ductular region, lack curative therapies and cause considerable mortality. Here we generated a high-definition spatiotemporal atlas of gene expression during cholestatic injury and repair in mice by integrating spatial enhanced resolution omics sequencing and single-cell transcriptomics. Spatiotemporal analyses revealed a key role of cholangiocyte-driven signaling correlating with the periportal damage-repair response. Cholangiocytes express genes related to recruitment and differentiation of lipid-associated macrophages, which generate feedback signals enhancing ductular reaction. Moreover, cholangiocytes express high TGFß in association with the conversion of liver progenitor-like cells into cholangiocytes during injury and the dampened proliferation of periportal hepatocytes during recovery. Notably, Atoh8 restricts hepatocyte proliferation during 3,5-diethoxycarbonyl-1,4-dihydro-collidin damage and is quickly downregulated after injury withdrawal, allowing hepatocytes to respond to growth signals. Our findings lay a keystone for in-depth studies of cellular dynamics and molecular mechanisms of cholestatic injuries, which may further develop into therapies for cholangiopathies.

A spatiotemporal atlas of mouse liver homeostasis and regeneration.

The mechanism by which mammalian liver cell responses are coordinated during tissue homeostasis and perturbation is poorly understood, representing a major obstacle in our understanding of many diseases. This knowledge gap is caused by the difficulty involved with studying multiple cell types in different states and locations, particularly when these are transient. We have combined Stereo-seq (spatiotemporal enhanced resolution omics-sequencing) with single-cell transcriptomic profiling of 473,290 cells to generate a high-definition spatiotemporal atlas of mouse liver homeostasis and regeneration at the whole-lobe scale. Our integrative study dissects in detail the molecular gradients controlling liver cell function, systematically defining how gene networks are dynamically modulated through intercellular communication to promote regeneration. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as a rheostat linking inflammation to Wnt/ß-catenin signaling for facilitating hepatocyte proliferation. Our data and analytical pipelines lay the foundation for future high-definition tissue-scale atlases of organ physiology and malfunction.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

Inhalation of 2, 4-di-tert-butylphenol-Loaded micelles suppresses respiratory syncytial virus infection in mice.

Human respiratory syncytial virus (RSV) is a common cause of respiratory infections in infants, young children, and elderly people. However, there are no effective treatments or vaccines available in most countries. In this study, we explored the anti-RSV potential of 2, 4-Di-tert-butylphenol (2, 4-DTBP), a compound derived from Houttuynia cordata Thunb. To overcome the poor solubility of 2, 4-DTBP, we encapsulated it in polymeric micelles and delivered it by inhalation. We found that 2, 4-DTBP-loaded micelles inhibited RSV infection in vitro and improved survival, lung pathology, and viral clearance in RSV-infected mice. Our results suggested that 2, 4-DTBP-loaded micelle is a promising novel therapeutic agent for RSV infection.

Experimental study of a canine model for a newly designed adjustable prefenestration aortic stent graft.

PURPOSE: When performing thoracic aortic endovascular repair (TEVAR) on lesions of the aortic arch, physician- modified fenestration or in situ fenestration is often used to maintain patent branches. We designed a new adjustable prefenestration aortic stent graft that can both isolate pathologies in the aortic arch and obtain patent branches simultaneously. In this study, we use this new type of stent to perform fenestrated TEVAR in a canine's aorta. This study aims to evaluate the safety and feasibility of the new device, which may provide preliminary data for potential human application. METHODS: Eight Labrador Retriever canines underwent fenestrated TEVAR using the new stent device. Digital subtract angiography (DSA) was performed before and after fenestrated TEVAR to evaluate the safety and feasibility of the procedure. For the device deployment, at the "large curvature" side in the endograft, there is a rectangular prefenestration area (2 × 5 cm) without the polytetrafluoroethylene membrane, and at both longer side edges of the fenestration, there are two slide rails. A moveable membrane that covers the same area as the prefenestration area is initially set at the prefenestration position. A stay line is connected from the distal site of the moveable membrane that controls it to the distal position along the slide rail, which releases the fenestration. After the positioning of the prefenestration is determined, the outer sheath of the delivery system is released, and the stay line at the end of the delivery system is pulled outside the body. The animals were divided into a 1-month group (n = 4) and a 3-month group (n = 4) after the fenestrated TEVAR. Computed tomography (CT) was performed before euthanasia, and video of the DSA during the procedures and CT angiography (CTA) images were then studied. RESULTS: The procedure success rate was 100%, but the total survival rate was only 87.5%. There were no aortic-related deaths during follow-up, and during the operation, there were no stent-graft-related accidents. In addition, no stent-graft migrations were observed in the CTA, and all branch arteries were kept patent by the adjustable fenestration. Finally, histological examination and electron microscope results showed no obvious vascular injury or inflammation. CONCLUSION: Based on the results of this study, we judge the safety and feasibility of the use of the newly designed adjustable prefenestration aortic stent graft in a fenestrated-TEVAR canine model to be acceptable. Our preliminary data may provide a first reference for evaluating the new stent's potential use in humans.

An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Cell atlas of CCl 4-induced progressive liver fibrosis reveals stage-specific responses.

Chronic liver injury leads to progressive liver fibrosis and ultimately cirrhosis, a major cause of morbidity and mortality worldwide. However, there are currently no effective anti-fibrotic therapies available, especially for late-stage patients, which is partly attributed to the major knowledge gap regarding liver cell heterogeneity and cell-specific responses in different fibrosis stages. To reveal the multicellular networks regulating mammalian liver fibrosis from mild to severe phenotypes, we generated a single-nucleus transcriptomic atlas encompassing 49 919 nuclei corresponding to all main liver cell types at different stages of murine carbon tetrachloride (CCl 4)-induced progressive liver fibrosis. Integrative analysis distinguished the sequential responses to injury of hepatocytes, hepatic stellate cells and endothelial cells. Moreover, we reconstructed cell-cell interactions and gene regulatory networks implicated in these processes. These integrative analyses uncovered previously overlooked aspects of hepatocyte proliferation exhaustion and disrupted pericentral metabolic functions, dysfunction for clearance by apoptosis of activated hepatic stellate cells, accumulation of pro-fibrotic signals, and the switch from an anti-angiogenic to a pro-angiogenic program during CCl 4-induced progressive liver fibrosis. Our dataset thus constitutes a useful resource for understanding the molecular basis of progressive liver fibrosis using a relevant animal model.

Treatment strategies for endoleak after endovascular repair of the abdominal aortic aneurysm: A single center retrospective study.

BACKGROUND: Endovascular abdominal aortic aneurysm repair (EVAR) is the most frequently used treatment for aneurysm in abdominal aorta. The endoleak after EVAR causes the aneurysm sac to remain enlarged and risk for rupture. AIMS: The purpose of the study was to assess the efficacy of strategies and techniques for endoleak treatment. METHODS: This study was a single center retrospective study of 30 patients who had kinds of endoleak. The 30 patients were from a cohort of 597 patients who received EVAR from the Secondary Xiangya Hospital, Central South University between Jan 2014 to Dec 2021, what is follow-up well and diagnosed as endoleak. Data included basic clinical information, aspects of the endoleak treatment techniques, and follow-up findings. RESULTS: The 30 patients with endoleak were diagnosed by computed tomography angiography or digital subtraction angiography. Age is 69 ± 7.9 yrs. 26 patients are male with only 4 female patients. Immediate endoleak after EVAR is 46.7%and delayed endoleak is 53.3%. The classification of endoleak is type Ⅰ:76.6%; type Ⅱ 26.7%; type Ⅲ:6.7%; type Ⅳ:6.7%; type Ⅴ:13.3%. Different treatment of endoleak includes: screening, endovascular re-intervention and open surgery. There are 3 patients (10.0%) underwent emergency EVAR due to their rupture condition of aneurysm. All the endoleak patients' CTA image characteristics has been reviewed. The follow-up rate is 93.3%. There are 6 patients (21.4%) died during follow-up. No aneurysm sac rupture death has been recorded. CONCLUSIONS: Endoleak after EVAR is the most frequent complication that directly affects survival and re-intervention rates. Our findings suggested that different treatment strategies based on the individual patient's situation is important for their endoleak treating result.

Animal study on adjustable pre - fenestration aortic stent - graft. / å¯è°ƒèŠ‚é¢„å¼€çª—ä¸»åŠ¨è„‰è¦†è†œæ”¯æž¶çš„åŠ¨ç‰©å®žéªŒç ”ç©¶.

OBJECTIVES: To isolate aortic arch pathologies and keep the branches superior in arch patent, it always need physicians to do in-vivo fenestration or in-situ fenestration when performing the thoracic endovascular aortic repair (TEVAR). However, both of those fenestration techniques need structure modification of the stent-graft, which may affect their long-term stability. We designed an adjustable pre-fenestration aortic stent-graft to treat pathologies in this area and obtained a patent branch arteries. This study used this new designed stent-graft to perform fenestrated-TEVAR (f-TEVAR) in canine aorta. This study aims to identify its feasibility and safety through animal experiments, which might provide preliminary data for potential human implantation. METHODS: A total of 8 Labrador Retrievers were underwent f-TEVAR by using the new devices. Digital subtraction angiography was performed before and after f-TEVAR to evaluate the success of the procedures. All the canines were divided into a 4-week group (feeding for 4 weeks after operation) and a 12-week group (feeding for 12 weeks after operation). Computed tomography angiography (CTA) were performed before euthanasia. RESULTS: The success rate of operation was 100%. During the operation, there was no accident of major bleeding or failure to be released by fenestration. Adjustable fenestration worked well. No stent-graft migration was found in CTA at 4 weeks and 12 weeks after the operation. All branch arteries kept by the adjustable fenestration were patent. CONCLUSIONS: The result of feasibility and safety of the new designed adjustable pre-fenestration aortic stent-graft in f-TEVAR of canine is acceptable. This study provides a reference for further optimization of this stent and human f-TEVAR implantation involving aortic arch lesions.

Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

Rolling back human pluripotent stem cells to an eight-cell embryo-like stage.

After fertilization, the quiescent zygote experiences a burst of genome activation that initiates a short-lived totipotent state. Understanding the process of totipotency in human cells would have broad applications. However, in contrast to in mice1,2, demonstration of the time of zygotic genome activation or the eight-cell (8C) stage in in vitro cultured human cells has not yet been reported, and the study of embryos is limited by ethical and practical considerations. Here we describe a transgene-free, rapid and controllable method for producing 8C-like cells (8CLCs) from human pluripotent stem cells. Single-cell analysis identified key molecular events and gene networks associated with this conversion. Loss-of-function experiments identified fundamental roles for DPPA3, a master regulator of DNA methylation in oocytes3, and TPRX1, a eutherian totipotent cell homeobox (ETCHbox) family transcription factor that is absent in mice4. DPPA3 induces DNA demethylation throughout the 8CLC conversion process, whereas TPRX1 is a key executor of 8CLC gene networks. We further demonstrate that 8CLCs can produce embryonic and extraembryonic lineages in vitro or in vivo in the form of blastoids5 and complex teratomas. Our approach provides a resource to uncover the molecular process of early human embryogenesis.

The tomato OST1-VOZ1 module regulates drought-mediated flowering.

Flowering is a critical agricultural trait that substantially affects tomato fruit yield. Although drought stress influences flowering time, the molecular mechanism underlying drought-regulated flowering in tomato remains elusive. In this study, we demonstrated that loss of function of tomato OPEN STOMATA 1 (SlOST1), a protein kinase essential for abscisic acid (ABA) signaling and abiotic stress responses, lowers the tolerance of tomato plants to drought stress. slost1 mutants also exhibited a late flowering phenotype under both normal and drought stress conditions. We also established that SlOST1 directly interacts with and phosphorylates the NAC (NAM, ATAF and CUC)-type transcription factor VASCULAR PLANT ONE-ZINC FINGER 1 (SlVOZ1), at residue serine 67, thereby enhancing its stability and nuclear translocation in an ABA-dependent manner. Moreover, we uncovered several SlVOZ1 binding motifs from DNA affinity purification sequencing analyses and revealed that SlVOZ1 can directly bind to the promoter of the major flowering-integrator gene SINGLE FLOWER TRUSS to promote tomato flowering transition in response to drought. Collectively, our data uncover the essential role of the SlOST1-SlVOZ1 module in regulating flowering in response to drought stress in tomato and offer insights into a novel strategy to balance drought stress response and flowering.

G protein coupled estrogen receptor attenuates mechanical stress-mediated apoptosis of chondrocyte in osteoarthritis via suppression of Piezo1.

BACKGROUND: Apoptosis of chondrocyte is involved in osteoarthritis (OA) pathogenesis, and mechanical stress plays a key role in this process by activation of Piezo1. However, the negative regulation of signal conduction mediated by mechanical stress is still unclear. Here, we elucidate that the critical role of G protein coupled estrogen receptor (GPER) in the regulation of mechanical stress-mediated signal transduction and chondrocyte apoptosis. METHODS: The gene expression profile was detected by gene chip upon silencing Piezo1. The expression of GPER in cartilage tissue taken from the clinical patients was detected by RT-PCR and Western blot as well as immunohistochemistry, and the correlation between GPER expression and OA was also investigated. The chondrocytes exposed to mechanical stress were treated with estrogen, G-1, G15, GPER-siRNA and YAP (Yes-associated protein)-siRNA. The cell viability of chondrocytes was measured. The expression of polymerized actin and Piezo1 as well as the subcellular localization of YAP was observed under laser confocal microscope. Western blot confirmed the changes of YAP/ Rho GTPase activating protein 29 (ARHGAP29) /RhoA/LIMK /Cofilin pathway. The knee specimens of osteoarthritis model were stained with safranin and green. OARSI score was used to evaluate the joint lesions. The expressions of GPER and YAP were detected by immunochemistry. RESULTS: Expression profiles of Piezo1- silenced chondrocytes showed that GPER expression was significantly upregulated. Moreover, GPER was negatively correlated with cartilage degeneration during OA pathogenesis. In addition, we uncovered that GPER directly targeted YAP and broadly restrained mechanical stress-triggered actin polymerization. Mechanism studies revealed that GPER inhibited mechanical stress-mediated RhoA/LIMK/cofilin pathway, as well as the actin polymerization, by promoting expression of YAP and ARHGAP29, and the YAP nuclear localization, eventually causing the inhibition of Piezo1. YAP was obviously decreased in degenerated cartilage. Silencing YAP caused significantly increased actin polymerization and activation of Piezo1, and an increase of chondrocyte apoptosis. In addition, intra-articular injection of G-1 to OA rat effectively attenuated cartilage degeneration. CONCLUSION: We propose a novel regulatory mechanism underlying mechanical stress-mediated apoptosis of chondrocyte and elucidate the potential application value of GPER as therapy targets for OA.

[Preparation and Evaluation of Intranasal in situ Gel of Bupleuri Radix Volatile Oil and Baicalin].

OBJECTIVE: To prepare and evaluate a new formulation of thermosensitive and ion-sensitive in situ gel for nasal administration, using the volatile oil of Bupleuri radix and baicalin, the effective component extracted from Scutellariae radix . METHODS: Formulation of in situ nasal gel of Bupleuri radix volatile oil and baicalin was prepared by using poloxamer 407 and deacetylated gellan gum as the gel base, 10% pharmasolve and 2% polysorbate 80 as the solubilizer, and 0.8% triethanolamine as the pH regulator. The physical appearance, phase transition temperature, and baicalin release performance of the prepared gel were examined. The pharmacodynamic evaluation was done with the rat fever model developed with dry yeast and the mouse auricle swelling inflammation model. RESULTS: The phase transition temperature of the gel was optimized to be 36 ℃. The release of baicalin from the gel showed obvious features of sustained release, which accorded well the zero-order kinetics equation. The results of experiments with the rat dry yeast fever model and the mouse xylene auricle swelling inflammation model showed that the gel had significant antipyretic and anti-inflammatory effects that were significantly better than those of the groups treated with the blank gel base and the Bupleuri radix and Scutellariae radix granule. Results from the cilia toxicity test showed that the gel did not have obvious toxic effect on toad palate mucosal cilia. CONCLUSION: The in situ nasal gel of Bupleuri radix volatile oil and baicalin prepared in the study had a rapid onset time, high efficiency, and prolonged release of active ingredients, thus showing promises for further applicational development.

Gas-Liquid Two-Phase Flow Pattern Identification of a Centrifugal Pump Based on SMOTE and Artificial Neural Network.

The accurate identification of the gas-liquid two-phase flow pattern within the impeller of a centrifugal pump is critical to develop a reliable model for predicting the gas-liquid two-phase performance of the centrifugal pump. The influences of the inlet gas volume fraction, the liquid phase flow rate and the pump rotational speed on the flow characteristics of the centrifugal pump were investigated experimentally. Four typical flow patterns in the impeller of the centrifugal pump, i.e., the bubble flow, the agglomerated bubble flow, the gas pocket flow and the segregated flow, were obtained, and the corresponding flow pattern maps were drawn. After oversampling based on the SMOTE algorithm, a four-layer artificial neural network model with two hidden layers was constructed. By selecting the appropriate network super parameters, including the neuron numbers in the hidden layer, the learning rate and the activation function, the different flow patterns in the centrifugal pump impeller were identified. The identification rate of the model increased from 89.91% to 94.88% when the original data was oversampled by the SMOTE algorithm. It is demonstrated that the SMOTE algorithm is an effective method to improve the accuracy of the artificial neural network model. In addition, the Kappa coefficient, the Macro-F1 and the Micro-F1 were 0.93, 0.95 and 0.95, respectively, indicating that the model established in this paper can well identify the flow pattern in the impeller of a centrifugal pump.