Optimization of nutrient management improves productivity, quality and sustainability of albino tea cultivar Baiye-1.

Proper nutrient management is crucially important to the sustainable development of tea production. Compared to normal green-leaf cultivars, albino tea cultivars produce green tea of superior quality characterized by high contents of amino acids as a result of the hydrolysis of chloroplast proteins at albinism. However, the advantage of albino tea cultivars was offset by inferior growth and yield performance because of low contents of chlorophylls and limited photosynthesis capacity. Our understanding about the nutrition characteristics of albino tea cultivars was very limited. A four-year field experiment was conducted to develop proper nutrient management for Baiye-1 to overcome its weakness of low productivity without a tradeoff in tea quality and environmental risks. The nutrient management schemes were formulated by optimizing the rate and ratio of nitrogen (N), phosphorus, potassium and magnesium together with substitution of chemical fertilizers with organic manures. The total amounts of nutrients in the optimized schemes were reduced by 25% compared to the local farmers' practice (FP). Results showed that optimized rates and ratio of nutrients together with partial substitution of chemical fertilizers with rapeseed cake manure more considerably improved albino tea yield, the contents of free amino acids, total polyphenol and catechins relative to FP. Partial substitution of chemical fertilizers with commercial livestock manure decreased tea quality, which was likely caused by a dilution effect of increasing tea yield and decreasing N status of tea plants. Full organic substitution of chemical fertilizers by rapeseed cake manure improved tea yield and quality but had relatively low agronomic efficiency and profit. The effect of optimized nutrient management schemes was associated with the improvement of nutritional status in tea plants. The present work demonstrated that the optimization of nutrient management considerably improved albino tea yield, quality and profit while decreased the application rate of fertilizers and the intensity of greenhouse gas emissions.

A blueprint for tumor-infiltrating B cells across human cancers.

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

Arthroscopic Resection for Extra-articular Ganglion Cysts of Gastrocnemius Near Vessels.

Extra-articular ganglion cysts arising from the gastrocnemius tendon near popliteal vessels can cause pain and claudication. Open resection of this kind of cyst has been described frequently because the vessels can be well protected with a retractor. However, it's a challenge to remove cysts that are near vessels under arthroscopy, because a retractor cannot be used in arthroscopic surgery. This article will report a method of arthroscopic resection for extra-articular ganglion cysts near popliteal vessels.

A Hybrid Scaffold Induces Chondrogenic Differentiation and Enhances In Vivo Cartilage Regeneration.

Extensively researched tissue engineering strategies involve incorporating cells into suitable biomaterials, offering promising alternatives to boost tissue repair. In this study, a hybrid scaffold, Gel-DCM, which integrates a photoreactive gelatin-hyaluronic acid hydrogel (Gel) with an oriented porous decellularized cartilage matrix (DCM), was designed to facilitate chondrogenic differentiation and cartilage repair. The Gel-DCM exhibited excellent biocompatibility in vitro, promoting favorable survival and growth of human adipose-derived stem cells (hADSCs) and articular chondrocytes (hACs). Gene expression analysis indicated that the hACs expanded within the Gel-DCM exhibited enhanced chondrogenic phenotype. In addition, Gel-DCM promoted chondrogenesis of hADSCs without the supplementation of exogenous growth factors. Following this, in vivo experiments were conducted where empty Gel-DCM or Gel-DCM loaded with hACs/hADSCs were used and implanted to repair osteochondral defects in a rat model. In the control group, no implants were delivered to the injury site. Interestingly, macroscopic, histological, and microcomputed tomography scanning results revealed superior cartilage restoration and subchondral bone reconstruction in the empty Gel-DCM group compared with the control group. Moreover, both hACs-loaded and hADSCs-loaded Gel-DCM implants exhibited superior repair of hyaline cartilage and successful reconstruction of subchondral bone, whereas defects in the control groups were predominantly filled with fibrous tissue. These observations suggest that the Gel-DCM can provide an appropriate three-dimensional chondrogenic microenvironment, and its combination with reparative cell sources, ACs or ADSCs, holds great potential for facilitating cartilage regeneration.

Fast and flexible profiling of chromatin accessibility and total RNA expression in single nuclei using Microwell-seq3.

Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

Construction of single-cell cross-species chromatin accessibility landscapes with combinatorial-hybridization-based ATAC-seq.

Despite recent advances in single-cell genomics, the lack of maps for single-cell candidate cis-regulatory elements (cCREs) in non-mammal species has limited our exploration of conserved regulatory programs across vertebrates and invertebrates. Here, we developed a combinatorial-hybridization-based method for single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) named CH-ATAC-seq, enabling the construction of single-cell accessible chromatin landscapes for zebrafish, Drosophila, and earthworms (Eisenia andrei). By integrating scATAC censuses of humans, monkeys, and mice, we systematically identified 152 distinct main cell types and around 0.8 million cell-type-specific cCREs. Our analysis provided insights into the conservation of neural, muscle, and immune lineages across species, while epithelial cells exhibited a higher organ-origin heterogeneity. Additionally, a large-scale gene regulatory network (GRN) was constructed in four vertebrates by integrating scRNA-seq censuses. Overall, our study provides a valuable resource for comparative epigenomics, identifying the evolutionary conservation and divergence of gene regulation across different species.

Single-cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer.

Highly aggressive gastric cancer (HAGC) is a gastric cancer characterized by bone marrow metastasis and disseminated intravascular coagulation (DIC). Information about the disease is limited. Here we employed single-cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single-cell RNA sequencing. The expression of genes of interest was validated by bulk RNA-sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2-like signature and T cells were suppressed and reduced in number. Analysis of cell-cell crosstalk revealed that several signalling pathways involved in neutrophil to T-cell suppression including APP-CD74, MIF-(CD74+CXCR2), and MIF-(CD74+CD44) pathways were increased in HAGC. NETosis-associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing.

BACKGROUND: Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. METHODS: RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. RESULTS: In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. CONCLUSIONS: We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Influence of Organic and Inorganic Fertilizers on Tea Growth and Quality and Soil Properties of Tea Orchards' Top Rhizosphere Soil.

Organic-based fertilizers have been ratified to be effective in ameliorating tea growth and the fertility of soil. However, the effect of integrated fertilization on tea growth and quality and the chemical properties of the soil in tea gardens are unclear. To address this, from 2020 to 2021, five different treatments were carried out in the greenhouse of the Tea Research Institute, Hangzhou, CAAS, including CK (control), NPK (chemical fertilizers), RC (rapeseed cake), NPK+B (chemical fertilizer + biochar), and NPK+RC, to investigate the effects of different fertilizations on soil chemistry and tea growth and quality. The results indicated that NPK+B and NPK+RC significantly improved the different amino acid and catechin concentrations in the young shoots, stems, and roots of the tea compared to the CK. The plant growth parameters, e.g., the plant height, no. of leaves, mid-stem girth, and fresh weights of stems and leaves, were significantly increased with integrated fertilization (NPK+B and NPK+RC) compared to the CK and solo organic and inorganic fertilizers. The chlorophyll contents (Chl a, Chl b, and Chl a+b) were generally higher with NPK+RC than with the CK (37%, 35%, and 36%), RC (14%, 26%, and 18%), and NPK (9%, 13%, and 11%) treatments. Integrated fertilization buffered the acidic soil of the tea garden and decreased the soil C:N ratio. NPK+RC also significantly increased the soil's total C (31% and 16%), N (43% and 31%), P (65% and 40%), available P (31% and 58%), K (70% and 25%), nitrate (504% and 188%), and ammonium (267% and 146%) concentrations compared to the CK and RC. The soil macro- (Mg and Ca) and micronutrients (Mn, Fe, Zn, and Cu) were significantly improved by the RC (100% and 72%) (49%, 161%, 112%, and 40%) and NPK+RC (88% and 48%) (47%, 75%, 45%, and 14%) compared to the CK. The chlorophyll contents and soil macro- and micronutrients were all significantly positively correlated with tea quality (amino acids and catechin contents) and growth. These results indicated that integrated fertilization improved the soil nutrient status, which is associated with the improvement of tea growth and quality. Thus, integrated nutrient management is a feasible tool for improving tea growth, quality, and low nutrient levels in the soil.

Cucumis sativus CsbZIP90 suppresses Podosphaera xanthii resistance by modulating reactive oxygen species.

Resistance to disease in plants requires the coordinated action of multiple functionally related genes, as it is difficult to improve disease resistance with a single functional gene. Therefore, the use of transcription factors to regulate the expression of multiple resistance genes to improve disease resistance has become a recent focus in the field of gene research. The basic leucine zipper (bZIP) transcription factor family plays vital regulatory roles in processes, such as plant growth and development and the stress response. In our previous study, CsbZIP90 (Cucsa.134370) was involved in the defense response of cucumber to Podosphaera xanthii, but the relationship between cucumber and resistance to powdery mildew remained unclear. Herein, we detected the function of CsbZIP90 in response to P. xanthii. CsbZIP90 was localized to the cytoplasm and nucleus, and its expression was significantly induced during P. xanthii attack. Transient overexpression of CsbZIP90 in cucumber cotyledons resulted in decreased resistance to P. xanthii, while silencing CsbZIP90 increased resistance to P. xanthii. CsbZIP90 negatively regulated the expression of reactive oxygen species (ROS)-related genes and activities of ROS-related kinases. Taken together, our results show that CsbZIP90 suppresses P. xanthi resistance by modulating ROS. This study will provide target genes for breeding cucumbers resistant to P. xanthii.

Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Target of rapamycin (TOR) plays a role in regulating ROS-induced chloroplast damage during cucumber (Cucumis sativus) leaf senescence.

In cucumber production, delaying leaf senescence is crucial for improving cucumber yield and quality. Target of rapamycin (TOR) is a highly conserved serine/threonine protein kinase in eukaryotes, which can integrate exogenous and endogenous signals (such as cell energy state levels) to stimulate cell growth, proliferation, and differentiation. However, no studies have yet examined the regulatory role of TOR signalling in cucumber leaf senescence. In this study, the effects of TOR signalling on dark-induced cucumber leaf senescence were investigated using the TOR activator MHY1485 and inhibitor AZD8055 combined with transient transformation techniques. The results indicate that TOR responds to dark-induced leaf senescence, and alterations in TOR activity/expression influence cucumber leaf resistance to dark-induced senescence. Specifically, in plants with elevated TOR activity/expression, we observed reduced expression of senescence-related genes, less membrane lipid damage, decreased cell apoptosis, lower levels of reactive oxygen species production, and less damage to the photosynthetic system compared to the control. In contrast, in plants with reduced TOR activity/expression, we observed higher expression of senescence-related genes, increased membrane lipid damage, enhanced cell apoptosis, elevated levels of reactive oxygen species production, and more damage to the photosynthetic system. These comprehensive results underscore the critical role of TOR in regulating dark-induced cucumber leaf senescence. These findings provide a foundation for controlling premature leaf senescence in cucumber production and offer insights for further exploration of leaf senescence mechanisms and the development of more effective control methods.

Au Doping PtNi Nanodendrites for Enhanced Electrocatalytic Methanol Oxidation Reaction.

To boost the electrocatalytic methanol oxidation reaction (MOR) of Platinum (Pt), making binary PtM (M = transition metals, for example, Fe, Cu, and Ni) with specific morphology is known as a promising method. Although great progress has been made in the synthesis of shaped PtM catalysts toward MOR, enhancing the catalytic performance of the PtM to enable it to be commercialized is still a hotspot. In this work, the Au-doped PtNi dendritic nanoparticles (Au-PtNi DNPs) were obtained by doping a small amount of gold (Au) into initially prepared PtNi DNPs, greatly improving their MOR catalytic activity and durability. The energy-dispersive X-ray spectroscopy mapping (EDXS) indicates that the surface of DNPs is mainly composed of Au dopant and PtNi, while the core is mainly Pt, indicating the formation of Au-doped PtNi/Pt core-shell-like DNP structures. The electrocatalytic performance of the prepared Au-PtNi DNPs with different compositions for the MOR was evaluated using cyclic voltammetry, chronoamperometry, and CO-stripping tests. The experimental findings indicate that the Au-PtNi DNPs showed better MOR performance in comparison with PtNi DNPs and commercial Pt catalysts. Among all the catalysts, 6% Au-PtNi DNPs showed 4.3 times improved mass catalytic activity for the MOR in comparison with commercial Pt catalysts. In addition, all the prepared Au-PtNi DNPs display a remarkable CO tolerance compared to that of PtNi DNPs and commercial Pt catalysts. The dendritic structure of Au-PtNi DNPs can effectively enhance catalytic performance, combined with the electronic effect of Au, Pt, and Ni.

Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau.

The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30-60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700-7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000-14,000 years; TIB-HAN, 7,200-10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1, whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.

Patterns and abiotic drivers of soil organic carbon in perennial tea (Camellia sinensis L.) plantation system of China.

Understanding soil organic carbon (SOC), the largest carbon (C) pool of a terrestrial ecosystem, is essential for mitigating climate change. Currently, the spatial patterns and drivers of SOC in the plantations of tea, a perennial leaf crop, remain unclear. Therefore, the present study surveyed SOC across the main tea-producing areas of China, which is the largest tea producer in the world. We analyzed the soil samples from tea plantations under different scenarios, such as provinces, regions [southwest China (SW), south China (SC), south Yangtze (SY), and north Yangtze (NY)], climatic zones (temperate, subtropical, and tropical), and cultivars [large-leaf (LL) and middle or small-leaf (ML) cultivars]. Preliminary analysis revealed that most tea-producing areas (45%) had SOC content ranging from 10 to 20 g kg-1. The highest SOC was recorded for Yunnan among the various provinces, the SW tea-producing area among the four regions, the tropical region among the different climatic zones, and the areas with LL cultivars compared to those with ML cultivars. Further Pearson correlation analysis demonstrated significant associations between SOC and soil variables and random forest modeling (RF) identified that total nitrogen (TN) and available aluminum [Ava(Al)] of soil explained the maximum differences in SOC. Besides, a large indirect effect of geography (latitude and altitude) on SOC was detected through partial least squares path modeling (PLS-PM) analysis. Thus, the study revealed a high spatial heterogeneity in SOC across the major tea-producing areas of China. The findings also serve as a basis for planning fertilization strategies and C sequestration policies for tea plantations.

DHA attenuates cartilage degeneration by mediating apoptosis and autophagy in human chondrocytes and rat models of osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease that usually occurs in the elderly, and docosahexaenoic acid (DHA) plays a therapeutic role in cardiovascular disease, diabetes, and rheumatoid arthritis (RA) with its anti-inflammatory and antioxidant effects. The objective of this study is to investigate the effect and mechanism of DHA on hypertrophic differentiation and senescence of OA chondrocytes to provide a theoretical basis for the effect of OA clinical treatment. A human OA chondrocyte model was established by IL-1ß, and a rat model of OA was established by anterior cruciate ligament (ACL) transection and medial meniscectomy. The result showed DHA promoted chondrocyte proliferation and reduced apoptosis. Transmission electron microscopy (TEM) analysis showed that there were more autophagosomes in the cytoplasm under the treatment of DHA. Compared to the OA group, samples from the OA + DHA group showed thickened cartilage, reduced degeneration, and an increased rate of collagen II-positive cells, while the Mankin score was significantly lower. In addition, DHA decreased the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and the ratio of light chain 3-I/II (LC3-I/II) and increased the expression of Beclin-1 and Bcl-2 measured by western blot analysis. Therefore, DHA promotes chondrocyte proliferation, reduces apoptosis, and increases autophagy in OA chondrocytes, a process that is accomplished by inhibiting the expression of mTOR, c-Jun N-terminal kinase (JNK), and p38 signaling pathways, providing new perspectives and bootstrap points for the prevention and treatment of OA.

Nitrogen addition reduces phosphorus availability and induces a shift in soil phosphorus cycling microbial community in a tea (Camellia sinensis L.) plantation.

Nitrogen (N) and phosphorus (P) are two important nutrient elements that limit the growth of plants and microorganisms. The effect of the N supply on soil P cycling and its mechanism remain poorly known. Here, we characterized the effects of different N application rates on soil P availability, the abundances of P-cycling functional genes, and microbial communities involved in P-cycling following the application of N for 13 years in a tea plantation. Soil available P (AP) decreased significantly under N application. The opposite pattern was observed for the activity of soil phosphatases including alkaline (ALP) and acid phosphatase (ACP). Furthermore, N addition increased the abundance of ppa but decreased the abundance of phoD in soil. Both ppa- and phoD-harboring communities varied with N application levels. Redundancy analysis (RDA) showed that soil pH was a key variable modulating ppa-harboring and phoD-harboring microbial communities. Partial least squares path modeling (PLS-PM) revealed that long-term N application indirectly reduced soil P availability by altering the abundances of phoD-harboring biomarker taxa. Overall, our findings indicated that N-induced reductions in AP increased microbial competition for P by selecting microbes with P uptake and starvation response genes or those with phosphatases in tea plantation system. This suggests that tea plantations should be periodically supplemented with P under N application, especially under high N application levels.

Gut microbiome alterations in pulmonary hypertension in highlanders and lowlanders.

Background: Alterations in the gut microbiota have been observed in patients with pulmonary hypertension (PH), though whether the roles of the gut microbiota in PH at different altitudes are the same is unknown. This study aims to evaluate the associations of the gut microbiome with PH in highlanders and lowlanders. Methods: PH patients and controls were recruited from those who permanently live on the Tibetan plateau (highlanders) or the plains (lowlanders), and underwent transthoracic echocardiography close to their altitude of residence (at 5070 m for highlanders versus6 m for lowlanders). The gut microbiome was profiled using metagenomic shotgun sequencing. Results: In total, 13 PH patients (46% highlanders) and 88 controls (70% highlanders) were included. The overall microbial composition was different in PH patients compared to controls (p=0.003). Notably, among lowlanders, a composite microbial score of pro-atherosclerotic trimethylamine-producing species was increased in PH patients compared with that in controls (p=0.028), while among highlanders no such difference was observed (p=0.087). Another composite gut microbial score including eight species of Lactobacillus, which has shown beneficial effects on cardiovascular functions, was higher in highlanders than lowlanders (p<0.01). Furthermore, this score tended to be lower in PH patients than controls among highlanders (p=0.056) but not among lowlanders (p=0.840). In addition, the gut microbiome showed a good performance in distinguishing PH patients from controls in both lowlanders and highlanders. Conclusions: Our study reported differently altered gut microbiome profiles between highland and lowland PH patients, highlighting the distinct microbial mechanism in PH in highlanders compared with lowlanders.

SnRK1 signaling regulates cucumber growth and resistance to Corynespora cassiicola.

Energy metabolism is one of the key factors determining the growth and development of plants and the response to biotic and abiotic stresses. Sucrose non-fermentation 1 related protein kinase 1 (SnRK1) is an important energy-sensitive regulator that plays a key role in the overall control of carbohydrate metabolism. However, little is known about the function of SnRK1 in cucumber. In this study, metformin (an SnRK1 activator) and trehalose (an SnRK1 inhibitor) were used to investigate the role of SnRK1 signaling in cucumber. The results showed that SnRK1 activation could inhibit the growth of cucumber, slow down the net photosynthetic rate (Pn), reduce the contents of photosynthetic pigments and soluble sugars, and suppress the expression of genes related to sucrose metabolism. By contrast, SnRK1 inhibition yielded opposite results. Furthermore, SnRK1 activation and CsSnRK1 over-expression improved cucumber resistance to Corynespora cassiicola. While, SnRK1 inhibition and CsSnRK1 silencing reduced the resistance of cucumber to C. cassiicola. The results indicated that CsSnRK1 gene can positively regulate the resistance of cucumber to C. cassiicola. We conclude that CsSnRK1 signaling plays an important role in balancing the growth and immune response of cucumber. These results can be applied to the improvement of disease-resistant cucumber varieties.

Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair.

Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture. Nowadays, the application of various stem cell sources, including mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), for tendon repair has shown great potential, because these cells can differentiate into a tendon lineage and promote functional tendon repair. However, the mechanism underlying tenogenic differentiation remains unclear. Moreover, no widely adopted protocol has been established for effective and reproducible tenogenic differentiation because of the lack of definitive biomarkers for identifying the tendon differentiation cascades. This work is aimed at reviewing the literature over the past decade and providing an overview of background information on the clinical relevance of tendons and the urgent need to improve tendon repair; the advantages and disadvantages of different stem cell types used for boosting tendon repair; and the unique advantages of reported strategies for tenogenic differentiation, including growth factors, gene modification, biomaterials, and mechanical stimulation.