Triple-Phosphorescent Gold Nanoclusters Enabled by Isomerization of Terminal Thiouracils in the Surface Motifs.

Metal nanoclusters (NCs) hold great promise for expressing multipeak emission based on their well-defined total structure with diverse luminescent centers. Herein, we report the surface motif-dictated triple phosphorescence of Au NCs with dynamic color turning. The deprotonation-triggered isomerization of terminal thiouracils can evolve into a mutual transformation among their hierarchical motifs, thus serving a multipeak-emission expression with good tailoring. More importantly, the underlying electron transfer is thoroughly identified by excluding the radiative and nonradiative energy transfer, where electrons flow from the first phosphorescent state to the last two ones. The findings shed light on finely tailing motifs at the molecular level to motivate studies on customizable luminescence characteristics of metal NCs.

High-resolution reconstruction of April-September precipitation and major extreme droughts in China over the past ∼530 years.

Extreme drought events have increased, causing serious losses and damage to the social economy under current warming conditions. However, short-term meteorological data limit our understanding and projection of these extremes. With the accumulation of proxy data, especially tree-ring data, large-scale precipitation field reconstruction has provided opportunities to explore underlying mechanisms further. Using point-by-point regression, we reconstructed the April-September precipitation field in China for the past ∼530 years on the basis of 590 proxy records, including 470 tree-ring width chronologies and 120 drought/flood indices. Our regression models explained average 50% of the variance in precipitation. In the statistical test on calibration and verification, our models passed the significance level that assured reconstruction quality. The reconstruction data performed well, showing consistency and better quality than previously reported reconstructions. The first three leading modes of variability in the reconstruction revealed the main distribution modes of precipitation over China. Wet/drought and extremely wet/drought years accounted for 12.81%/10.92% (68 years/58 years) and 1.69%/3.20% (9 years/17 years) of the past ∼530 years in China, respectively. Major extreme drought events can be identified explicitly in our reconstruction. The detailed features of the Chongzhen Great Drought (1637-1643), the Wanli Great Drought (1585-1590), and the Ding-Wu Great Famine (1874-1879), indicated the existence of potentially different underlying mechanisms that need further exploration. Although further improvements can be made for remote uninhabited areas and large deserts, our gridded reconstruction of April-September precipitation in China over the past ∼530 years can provide a solid database for studies on the attribution of climate change and the mechanism of extreme drought events.

Anterolateral femoral interregional flap with turbocharge technique versus traditional anterolateral femoral flap in the repair of limblarge wound surface. / ç»“åˆå† å¢žåŽ‹æŠ€æœ¯çš„è‚¡å‰å¤–ä¾§è·¨åŒºçš®ç“£ä¿®å¤è‚¢ä½“è¾ƒå¤§åˆ›é¢ä¸´åºŠç ”ç©¶.

OBJECTIVES: To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of limblarge wound surface. METHODS: Clinical data of 38 patients withlimb large wound surface (11 cm×39 cm-16 cm× 65 cm) admitted to the Department of Prosthetics and Reconstruction of Sir Run Run Shaw Hospital from May 2018 to May 2022 were retrospectively analyzed. Eighteen patients were treated by anterolateral femoral perforator flap and superficial circumflex iliac artery flap (ALTP-SCIAP) with turbocharge technique (interregional flap group); while 20 patients were treated with unilateral or bilateral anterolateral femoral flaps, combined with skin grafting if necessary (traditional anterolateral femoral flap group). The survival of skin flap, repair of donor area, complications and patient satisfaction were compared between the two groups. RESULTS: In interregional flap group, 18 flaps were harvested and transplanted, the flap width, length and the viable area were (9.9±2.0) cm, (44.2±3.5) cm and (343.2±79.9) cm2, respectively. In traditional anterolateral femoral flap group and 29 flaps were harvested and transplanted, the flap width, length and the viable area were (11.0-2.8) cm (21.7-3.2) cm and (186.4-49.2) cm2, respectively. There were significant differences in the flap length and survival area between the two groups (t=22.365 and 8.345, P<0.05), but not significant difference in the flap width (t=1.525, P>0.05). In the interregional flap group, the donor site of flap was closed by direct suture in 11 cases, by skin retractor assisted suture in 6 cases, and by skin grafting in 1 case. In traditional anterolateral femoral flap group, the donor site of flap was closed by direct suture in 12 flaps, by skin retractor assisted suture in 11 flaps, and by skin grafting in 6 flaps. No significant difference was found between the two groups (χ2=2.657, P>0.05). The interregional flap group had lower postoperative complications rate (5.6% vs. 35.0%, χ2=4.942, P<0.05) and higher patient satisfaction rate (94.4% vs. 70.0%, χ2=4.448, P<0.05) than traditional anterolateral femoral flap group. CONCLUSIONS: Compared with the traditional anterolateral thigh flap, the anterolateral femoral interregional flap with turbocharge technique has a larger flap area, less complications, and higher patient satisfaction rate. With sacrificing only one donor area and sharing a set of vascular pedicles, it can repair "super long", "super large" or irregular limb wound defects maximally. At the same time, most of the donor areas of the flap can be sutured directly without skin grafting.

Comprehensive evaluation of phosphate deficiency tolerance in common vetch germplasms and the adaption mechanism to phosphate deficiency.

Common vetch (Vicia sativa L.) is widely planted as forage, green manure and food. Phosphate (Pi) deficiency is an important constraint for legume crop production. In this study, P-deficiency tolerance in 40 common vetch collections was evaluated under hydroponic condition. The collections were clustered into three groups based on the tolerance level. Physiological responses to P-deficiency in two tolerant collections (418 and 426) in comparison with one sensitive collection (415) were investigated. Greater growth inhibition was observed in sensitive collection compared with two tolerant collections, although the inorganic phosphorus (P) content in sensitive collection was higher than those in tolerant collections. The internal and external purple acid phosphatase activity in plants showed no significant difference between 418 and 415 under low phosphate condition. Transcriptomic analysis in the tolerant collection 426 in response to Pi starvation showed that many common adaptive strategies were applied and PHOSPHATE STARVATION RESPONSE (PHR)-related Pi signaling and transporter genes were altered. VsPHT1.2 had the highest expression level in root among all VsPHT1s, and it was remarkably upregulated after short time of P-deficiency treatment in tolerant collections compared with sensitive collection. In conclusion, common vetch response to P starvation by altering the expressions of core genes involved in Pi transport and signaling, and the elevated expression of VsPHT1.2 gene might contribute to higher Pi acquisition efficiency in P-deficiency tolerant collections.

Spectral fusion-based machine learning classifiers for discriminating membrane breakage in multiple scenarios.

Membrane breakage can lead to filtration failure, which allows harmful substances to enter the effluent, posing potential hazards to human health and the environment. This study is an innovative combination of fluorescence and ultraviolet-visible (UV-Vis) spectroscopy to identify membrane breakage. It aims to unravel more comprehensive information, improve detection sensitivity and selectivity, and enable real-time monitoring capabilities. Fluorescence and UV-Vis data are extracted through variance partitioning analysis (VPA) and integrated through a decision tree algorithm to form a superior system with enhanced discrimination capabilities. VPA improves discrimination efficiency by extracting key information from spectral data and eliminating redundancy. The decision tree algorithm, on the other hand, can process large amounts of data simultaneously. In addition, the method has a wide range of applications and can be used in various scenarios accurately. The scenarios include domestic sewage, micropollutant water, aquaculture wastewater, and secondary treated sewage. The experimental results validate the application of machine learning classifiers in membrane breakage detection with an accuracy rate of 96.8 % to 97.4 %.

Radiation-primed TGF-ß trapping by engineered extracellular vesicles for targeted glioblastoma therapy.

The poor outcome of glioblastoma multiforme (GBM) treated with immunotherapy is attributed to the profound immunosuppressive tumor microenvironment (TME) and the lack of effective delivery across the blood-brain barrier. Radiation therapy (RT) induces an immunogenic antitumor response that is counteracted by evasive mechanisms, among which transforming growth factor-ß (TGF-ß) activation is the most prominent factor. We report an extracellular vesicle (EV)-based nanotherapeutic that traps TGF-ß by expressing the extracellular domain of the TGF-ß type II receptor and targets GBM by decorating the EV surface with RGD peptide. We show that short-burst radiation dramatically enhanced the targeting efficiency of RGD peptide-conjugated EVs to GBM, while the displayed TGF-ß trap reversed radiation-stimulated TGF-ß activation in the TME, offering a synergistic effect in the murine GBM model. The combined therapy significantly increased CD8+ cytotoxic T cells infiltration and M1/M2 macrophage ratio, resulting in the regression of tumor growth and prolongation of overall survival. These results provide an EV-based therapeutic strategy for immune remodeling of the GBM TME and eradication of therapy-resistant tumors, further supporting its clinical translation.

Efficacy and Safety of Atezolizumab and Bevacizumab in Appendiceal Adenocarcinoma.

PURPOSE: Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously. EXPERIMENTAL DESIGN: We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA. RESULTS: Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041). CONCLUSIONS: In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted. SIGNIFICANCE: AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study.

Tree-ring based summer temperature variability since 1790 CE in the Hindu Kush region of northern Pakistan.

The Hindu Kush high-altitude regions of Pakistan are currently experiencing severe consequences as a result of global warming. In this sense, increasing soil erosion and the quick melting of glaciers are two particularly evident effects. In such a scenario, understanding long-term temperature changes is crucial for making accurate forecasts about how the Hindu Kush region may experience regional temperature changes in the future. In this study, the climate tree-ring width (TRW) analysis designated a positive and significant correlation (r = 0.622, p < 0.001) between the TRW chronology and the June to September (summer) mean maximum temperature (MMT). Using the tree-ring width of Pinus wallichiana A. B. Jackson, we reconstructed summer temperatures in the Hindu Kush region from 1790 CE. Statistical analysis showed that the reconstruction model has explained 38.7% of the climate variance during the instrumental period of 1967 to 2018 CE. Five extremely warm summer periods (≥ 4 years; before the instrumental period 1967-2018 CE) of 1804-1830, 1839-1862, 1876-1879, 1905-1910, 1923-1935 CE, and six cold summer periods of 1790-1803, 1832-1838, 1863-1875, 1880-1904, 1911-1922, and 1936-1945 CE have been observed during the past 229 years. Individually, the year 1856 CE experienced severe warmth (31.85 °C), whereas 1794 CE was relatively cooler (29.60 °C). The spectral multi-taper method (MTM) shows significant (p < 0.05) cycles, which take place about every 9.3, 5.7, 4.2, and 3.6 years. In particular, the 9.3-year cycle, which closely aligns with the 11-year solar activity cycle, suggests a potential correlation between solar activity and local temperature fluctuations. Moreover, our reconstruction demonstrates a significant degree of consistency when compared to actual climate data and regional temperature reconstruction series, reporting a strong logic of trust in the reliability and accuracy of our findings. This evidence reaffirms that our reconstruction shows significant and dependable regional temperature signals, notably being representative for the Hindu Kush region.

Density-dependent species interactions modulate alpine treeline shifts.

Species interactions such as facilitation and competition play a crucial role in driving species range shifts. However, density dependence as a key feature of these processes has received little attention in both empirical and modelling studies. Herein, we used a novel, individual-based treeline model informed by rich in situ observations to quantify the contribution of density-dependent species interactions to alpine treeline dynamics, an iconic biome boundary recognized as an indicator of global warming. We found that competition and facilitation dominate in dense versus sparse vegetation scenarios respectively. The optimal balance between these two effects was identified at an intermediate vegetation thickness where the treeline elevation was the highest. Furthermore, treeline shift rates decreased sharply with vegetation thickness and the associated transition from positive to negative species interactions. We thus postulate that vegetation density must be considered when modelling species range dynamics to avoid inadequate predictions of its responses to climate warming.

Zinc finger transcription factor MtZPT2-2 negatively regulates salt tolerance in Medicago truncatula.

Zinc finger proteins (ZFPs) are transcription factors involved in multiple cellular functions. We identified a C2H2 type ZFP (MtZPT2-2) in Medicago truncatula and demonstrated that it localizes to the nucleus and inhibits the transcription of 2 genes encoding high-affinity potassium transporters (MtHKT1;1 and MtHKT1;2). MtZPT2-2 transcripts were detected in stem, leaf, flower, seeds and roots, with the highest level in the xylem and phloem of roots and stems. MtZPT2-2 transcription in leaves was reduced after salt stress. Compared with the wild-type (WT), transgenic lines overexpressing MtZPT2-2 had decreased salt tolerance, while MtZPT2-2-knockout mutants showed increased salt tolerance. MtHKT1;1 and MtHKT1;2 transcripts and Na+ accumulation in shoots and roots, as well as in the xylem of all genotypes of plants, were increased after salt treatment, with higher levels of MtHKT1;1 and MtHKT1;2 transcripts and Na+ accumulation in MtZPT2-2-knockout mutants and lower levels in MtZPT2-2-overexpressing lines compared with the WT. K+ levels showed no significant difference among plant genotypes under salt stress. Moreover, MtZPT2-2 was demonstrated to bind with the promoter of MtHKT1;1 and MtHKT1;2 to inhibit their expression. Antioxidant enzyme activities and the gene transcript levels were accordingly upregulated in response to salt, with higher levels in MtZPT2-2-knockout mutants and lower levels in MtZPT2-2-overexpressing lines compared with WT. The results suggest that MtZPT2-2 regulates salt tolerance negatively through downregulating MtHKT1;1 and MtHKT1;2 expression directly to reduce Na+ unloading from the xylem and regulates antioxidant defense indirectly.

In Situ Construction of Near-Infrared Response Hybrid Up-Conversion Photocatalyst for Degrading Organic Dyes and Antibiotics.

Unique nonlinear optical properties for converting low-energy incident light into high-energy radiation enable up-conversion materials to be employed in photocatalytic systems. An efficient near-infrared (NIR) response photocatalyst was successfully fabricated through a facile two-step method to load BiOBr on the Nd3+, Er3+@NaYF4 (NE@NYF) up-conversion material. The NE@NYF can transform NIR into visible and UV light and promote charge-energy transfer in the semiconductor. Consequently, the as-obtained photocatalysts exhibit excellent photodegradation performance for rhodamine B dye (RhB) and tetracycline (TC) organic pollutants. About 98.9% of the RhB was decomposed within 60 min with the 20% NE@NYF-B sample, outperforming the pristine BiOBr (61.9%). In addition, the 20% NE@NYF-B composite could decompose approximately 72.7% of the organic carbon during a 10 h reaction, which was almost two-fold more than that of BiOBr. Meanwhile, a possible charge transfer mechanism is proposed based on the recombination of electron-hole pairs and reactive oxygen species. This work provides a rational hybrid structure photocatalyst for improving photocatalytic performance in the broadband spectrum and provides a new strategy for NIR light utilization.

Warming-induced phenological mismatch between trees and shrubs explains high-elevation forest expansion.

Despite the importance of species interaction in modulating the range shifts of plants, little is known about the responses of coexisting life forms to a warmer climate. Here, we combine long-term monitoring of cambial phenology in sympatric trees and shrubs at two treelines of the Tibetan Plateau, with a meta-analysis of ring-width series from 344 shrubs and 575 trees paired across 11 alpine treelines in the Northern Hemisphere. Under a spring warming of +1°C, xylem resumption advances by 2-4 days in trees, but delays by 3-8 days in shrubs. The divergent phenological response to warming was due to shrubs being 3.2 times more sensitive than trees to chilling accumulation. Warmer winters increased the thermal requirement for cambial reactivation in shrubs, leading to a delayed response to warmer springs. Our meta-analysis confirmed such a mechanism across continental scales. The warming-induced phenological mismatch may give a competitive advantage to trees over shrubs, which would provide a new explanation for increasing alpine treeline shifts under the context of climate change.

SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma.

PURPOSE: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it. EXPERIMENTAL DESIGN: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC. RESULTS: ATR inhibition activated the cyclic GMP-AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)-dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory cytokines and immune checkpoints. Among the common RCC genotypes, SETD2 loss is associated with preferential ATR activation and sensitizes cells to ATR inhibition. SETD2 knockdown promoted the cytosolic DNA-sensing pathway in response to ATR inhibition. Treatment with the ATR inhibitor VE822 concurrently upregulated immune cell infiltration and immune checkpoint expression in Setd2 knockdown Renca tumors, providing a rationale for ATR inhibition plus ICB combination therapy. Setd2-deficient Renca tumors demonstrated greater vulnerability to ICB monotherapy or combination therapy with VE822 than Setd2-proficient tumors. Moreover, SETD2 mutations were associated with a higher response rate and prolonged overall survival in patients with ICB-treated RCC but not in patients with non-ICB-treated RCC. CONCLUSIONS: SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in patients with RCC with SETD2 mutations.

Jasmonate biosynthesis enzyme allene oxide cyclase 2 mediates cold tolerance and pathogen resistance.

Allene oxide cyclase (AOC) is a key enzyme in the biosynthesis of jasmonic acid (JA), which is involved in plant growth and development as well as adaptation to environmental stresses. We identified the cold- and pathogen-responsive AOC2 gene from Medicago sativa subsp. falcata (MfAOC2) and its homolog MtAOC2 from Medicago truncatula. Heterologous expression of MfAOC2 in M. truncatula enhanced cold tolerance and resistance to the fungal pathogen Rhizoctonia solani, with greater accumulation of JA and higher transcript levels of JA downstream genes than in wild-type plants. In contrast, mutation of MtAOC2 reduced cold tolerance and pathogen resistance, with less accumulation of JA and lower transcript levels of JA downstream genes in the aoc2 mutant than in wild-type plants. The aoc2 phenotype and low levels of cold-responsive C-repeat-binding factor (CBF) transcripts could be rescued by expressing MfAOC2 in aoc2 plants or exogenous application of methyl jasmonate. Compared with wild-type plants, higher levels of CBF transcripts were observed in lines expressing MfAOC2 but lower levels of CBF transcripts were observed in the aoc2 mutant under cold conditions; superoxide dismutase, catalase, and ascorbate-peroxidase activities as well as proline concentrations were higher in MfAOC2-expressing lines but lower in the aoc2 mutant. These results suggest that expression of MfAOC2 or MtAOC2 promotes biosynthesis of JA, which positively regulates expression of CBF genes and antioxidant defense under cold conditions and expression of JA downstream genes after pathogen infection, leading to greater cold tolerance and pathogen resistance.

Highly Water-Stable and Efficient Hydrogen-Producing Heterostructure Synthesized from Mn0.5Cd0.5S and a Zeolitic Imidazolate Framework ZIF-8 via Ligand and Cation Exchange.

Developing highly water-stable zeolitic imidazolate frameworks (ZIFs) for visible-light-driven photocatalytic hydrolysis is important and challenging. Herein, the Type II heterojunction catalyst Mn0.5Cd0.5S@ZIF-8 and its derivatives (including MCS@ZIF-8-Mn, MCS@ZIF-8-Br, and MCS@ZIF-8-MB) were successfully constructed using a facile strategy. Through dual postsynthetic ligand and cation exchange (PSE) treatments of Mn(Ac)2·4H2O and 4-bromo-1H-imidazole for ZIF-8, the hydrogen production efficiency of the MCS@ZIF-8-MB heterojunction catalyst can reach 5.450 mmol·g-1·h-1 and remain at 97.11% after 9 h of the stability test. Construction of heterojunctions can effectively improve the hydrogen production performance of Mn0.5Cd0.5S while maintaining excellent water stability. X-ray photoelectron spectroscopy results show that upon successful construction of the MCS@ZIF-8-MB heterojunction an interface forms between the surface of MCS and ZIF-8-MB, effectively weakening the photocorrosion of MCS. Density functional theory calculations also indicate that the induction of Mn can increase the electronic states of p and d orbitals near the Fermi level of ZIF-8, suggesting that Mn(II) attracts more electrons than Zn(II). This provides more powerful theoretical evidence for the electron cloud shift from the electron donor S2- to Mn2+.

Genome-Wide Analysis of the Wall-Associated Kinase (WAK) Genes in Medicago truncatula and Functional Characterization of MtWAK24 in Response to Pathogen Infection.

The wall-associated kinases (WAKs) can perceive and transmit extracellular signals as one kind of unique receptor-like kinases (RLKs) involved in the regulation of cell expansion, pathogen resistance and abiotic stress tolerance. To understand their potential roles and screen some key candidates in Medicago truncatula (M. truncatula), genome-wide identification and characterization of MtWAKs were conducted in this study. A total of 54 MtWAK genes were identified and classified into four groups based on their protein domains. They were distributed on all chromosomes, while most of them were clustered on chromosome 1 and 3. The synteny analysis showed that 11 orthologous pairs were identified between M. truncatula and Arabidopsis thaliana (A. thaliana) and 31 pairs between M. truncatula and Glycine max (G. max). The phylogenetic analysis showed that WAK-RLKs were classified into five clades, and they exhibited a species-specific expansion. Most MtWAK-RLKs had similar exon-intron organization and motif distribution. Multiple cis-acting elements responsive to phytohormones, stresses, growth and development were observed in the promoter regions of MtWAK-RLKs. In addition, the expression patterns of MtWAK-RLKs varied with different plant tissues, developmental stages and biotic and abiotic stresses. Interestingly, plasm membrane localized MtWAK24 significantly inhibited Phytophthora infection in tobacco. The study provides valuable information for characterizing the molecular functions of MtWAKs in regulation of plant growth, development and stress tolerance in legume plants.

The effects of water-based exercise on body composition: A systematic review and meta-analysis.

AIMS: This study aimed to investigate the effects of water-based exercise (WBE) on body composition. METHODS: Trials published up to October 28, 2022 were searched using the PubMed, EMBASE, Web of Science, Cochrane, Scopus, and Ovid databases. Randomized controlled trials of healthy adults published in English, comparing WBE and control groups, were included. Other studies with different research designs and participants with medical diagnoses were excluded. The main outcome measures were body weight (BW), body fat mass (BFM), body fat percentage (BFP), lean mass (LM), and skeletal muscle mass (SMM). RESULTS: Overall, 17,458 potential studies were identified. After a closer inspection, 79 full-length articles were considered for further screening. Finally, 20 studies, involving 565 participants, were included in the meta-analysis. The WBE was beneficial in reducing BW, BFM, and BFP and increasing LM and SMM. Subgroup analyses were conducted based on different exercise intensities and times per week. Moderate- or moderate-vigorous-intensity exercise helped improve body composition, while lower-intensity WBE or aquatic high-intensity interval training (HIIT) seemed less helpful. Training for <120 min/week was insufficient to improve body composition. Training for >120 min/week was associated with improvements in body composition. CONCLUSIONS: Moderate- or moderate-vigorous-intensity WBE helps improve body composition. Adults are encouraged to exercise for >120 min/week.

Isolation and identification of mycorrhizal helper bacteria of Vaccinium uliginosum and their interaction with mycorrhizal fungi.

Mycorrhizal helper bacteria (MHB) can promote mycorrhizal fungal colonization and form mycorrhizal symbiosis structures. To investigate the effect of interactions between mycorrhizal beneficial microorganisms on the growth of blueberry, 45 strains of bacteria isolated from the rhizosphere soil of Vaccinium uliginosum were screened for potential MHB strains using the dry-plate confrontation assay and the bacterial extracellular metabolite promotion method. The results showed that the growth rate of mycelium of Oidiodendron maius 143, an ericoid mycorrhizal fungal strain, was increased by 33.33 and 77.77% for bacterial strains L6 and LM3, respectively, compared with the control in the dry-plate confrontation assay. In addition, the extracellular metabolites of L6 and LM3 significantly promoted the growth of O. maius 143 mycelium with an average growth rate of 40.9 and 57.1%, respectively, the cell wall-degrading enzyme activities and genes of O. maius 143 was significantly increased. Therefore, L6 and LM3 were preliminarily identified as potential MHB strains. In addition, the co-inoculated treatments significantly increased blueberry growth; increased the nitrate reductase, glutamate dehydrogenase, glutamine synthetase, and glutamate synthase activities in the leaves; and promoted nutrient uptake in blueberry. Based on the physiological, and 16S rDNA gene molecular analyses, we initially identified strain L6 as Paenarthrobacter nicotinovorans and LM3 as Bacillus circulans. Metabolomic analysis revealed that mycelial exudates contain large amounts of sugars, organic acids and amino acids, which can be used as substrates to stimulate the growth of MHB. In conclusion, L6 and LM3 and O. maius 143 promote each other's growth, while co-inoculation of L6 and LM3 with O. maius 143 can promote the growth of blueberry seedlings, providing a theoretical basis for further studies on the mechanism of ericoid mycorrhizal fungi-MHB-blueberry interactions. It laid the technical foundation for the exploitation of biocontrol strain resources and the development of biological fertilizer.

High-Performance Multi-Dynamic Bond Cross-Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene-Cell Combination Therapy of Intervertebral Disc Degeneration.

Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene-cell combination therapy of IVDD. Phenylboronic acid-modified G5 PAMAM (G5-PBA) is first synthesized, and therapeutic siRNA silencing the expression of P65 mixed with G5-PBA (siRNA@G5-PBA) is then embedded into the hydrogel (siRNA@G5-PBA@Gel) based on multi-dynamic bonds including acyl hydrazone bonds, imine linkage, π-π stacking, and hydrogen bonding interactions. Local and acidic inflammatory microenvironment-responsive gene-drug release can achieve spatiotemporal regulation of gene expression. In addition, gene-drug release from the hydrogel can be sustained for more than 28 days in vitro and in vivo, greatly inhibiting the secretion of inflammatory factors and the subsequent degeneration of nucleus pulposus (NP) cells induced by lipopolysaccharide (LPS). Through prolonged inhibition of the P65/NLRP3 signaling pathway, the siRNA@G5-PBA@Gel is verified to relieve inflammatory storms, which can significantly enhance the regeneration of IVD when combined with cell therapy. Overall, this study proposes an innovative system for gene-cell combination therapy and a precise and minimally invasive treatment method for IVD regeneration.

Soluble Guanylate Cyclase ß1 Subunit Represses Human Glioblastoma Growth.

Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGCß1 alone repressed the aggressive course of glioma. The antitumor effect of sGCß1 was not associated with enzymatic activity of sGC since overexpression of sGCß1 alone did not influence the level of cyclic GMP. Additionally, sGCß1-induced inhibition of the growth of glioma cells was not influenced by treatment with sGC stimulators or inhibitors. The present study is the first to reveal that sGCß1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGCß1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCß1 overexpression impacted signaling in glioblastoma multiforme, including the promotion of nuclear accumulation of p53, a marked reduction in CDK6, and a significant decrease in integrin α6. These anticancer targets of sGCß1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment.