Search

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., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objectives: To compare the clinical outcomes of anterolateral femoral interregional flap with turbocharge technique and traditional anterolateral femoral flap in repair of large limb wounds., Methods: Clinical data of 38 patients with large limb surface wound (11 cm×39 cm-16 cm×65 cm) admitted to the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from May 2018 to May 2022 were retrospectively analyzed. Eighteen patients were treated by anterolateral thigh perforator flap combined with 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) cm 2 , respectively. In traditional anterolateral femoral flap group, 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) cm 2 , respectively. There were significant differences in the flap length and the viable area between the two groups ( t =22.365 and 8.345, both P <0.05). In the interregional flap group, the donor site of flap was closed by direct suture in 11 flaps, by skin retractor assisted suture in 6 flaps, and by skin grafting in one flap. 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. The skin graft rates of the two groups were 5.6% (1/18) and 20.7% (6/29), respectively ( χ 2 =2.007, P >0.05). The interregional flap group had lower postoperative complications rate (5.6% vs. 35.0%, χ 2 =4.942, P <0.05) and higher patient satisfaction rate (94.4% vs. 70.0%, χ 2 =4.448, P <0.05) than traditional anterolateral femoral flap group., Conclusions: Compared with the traditional anterolateral femoral flap, the anterolateral femoral interregional flap with turbocharge technique has a larger flap area, most of the donor areas of the flap can be sutured directly without skin grafting and with less complications and a higher patient satisfaction rate.

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.

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., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

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 %., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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-β (TGF-β) activation is the most prominent factor. We report an extracellular vesicle (EV)-based nanotherapeutic that traps TGF-β by expressing the extracellular domain of the TGF-β 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-β trap reversed radiation-stimulated TGF-β 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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024 The Authors; Published by the American Association for Cancer Research.)

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., (© 2024 John Wiley & Sons Ltd.)

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., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (©2023 American Association for Cancer Research.)

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., Competing Interests: Conflict of interest statement. The authors declare that they have no conflict of interest., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 Nd 3+ , Er 3+ @NaYF 4 (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.

Developing highly water-stable zeolitic imidazolate frameworks (ZIFs) for visible-light-driven photocatalytic hydrolysis is important and challenging. Herein, the Type II heterojunction catalyst Mn 0.5 Cd 0.5 S@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 ·4H 2 O and 4-bromo-1 H -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 Mn 0.5 Cd 0.5 S 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 S 2- to Mn 2+ .

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., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

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., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Dong, Zhang, Jiang, Zhu, Yang and Li.)

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 sGCβ1 alone repressed the aggressive course of glioma. The antitumor effect of sGCβ1 was not associated with enzymatic activity of sGC since overexpression of sGCβ1 alone did not influence the level of cyclic GMP. Additionally, sGCβ1-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 sGCβ1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGCβ1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCβ1 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 sGCβ1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment.

Longan ( Dimocarpus Longan ) is one of the most important fruit crops in Southern China. Lack of available Mg in acidic soil conditions is a limitation to further increasing longan yield. Magnesium transporter (MGT/MRS2) mediates the uptake, transport, and redistribution of Mg2+ in higher plants. To understand the role of MGTs family members in longan Mg deficiency. We identified and analyzed the protein characteristics, phylogeny, expression changes, subcellular localization, and transcriptional regulation of DlMGTs members. The results showed that, twelve DlMGTs are localized in the cell membrane, chloroplast, and nucleus. The evolutionary differences in MGTs between herbaceous and woody species in different plants. The DlMGTs promoters contained many cis-acting elements and transcription factor binding sites related to the hormone, environmental, and stress response. Subcellular localization assays showed that DlMGT1 localizes in the cell membrane of Arabidopsis protoplasts. The candidate transcription factor DlGATA16, which may regulate the expression of DlMGT1, was localized in the nucleus of tobacco leaves. Dual luciferase analysis demonstrated that DlGATA16 is a potential factor regulating the transcriptional activity of DlMGT1. In this study, we identified and analyzed DlMGTs on a genome-wide scale and the subcellular localization and interaction of DlMGT1 and DlGATA16, which has important implications for further functional analysis studies of MGTs and the use of MGT for longan genetic improvement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lv, Huang, Wang, Han, Li, Guo and Zhu.)

Aggregation-induced emission (AIE)-type metal nanoclusters (NCs) represent an innovative type of luminescent metal NCs whose aggregates exhibit superior performance over that of individuals, attracting wide attention over the past decade. Here, we give a concise overview of the progress made in this area, from design strategies to applications. The representative design strategies, including solvent-induction, cation-induction, crystallization-induction, pH-induction, ligand inheritance, surface constraint, and minerals- and MOF-confinement, are first discussed. We then present the typical practical applications of AIE-type metal NCs in the various sectors of bioimaging, biological diagnosis and therapy (e.g., antibacterial agents, cancer radiotherapy), light-emitting diodes (LEDs), detection assays, and circularly polarized luminescence (CPL). To this end, we present our viewpoints on the promises and challenges of AIE-type metal NCs, which may shed light on the design of highly luminescent metal NCs, stimulating new vitality and serving as a continuous boom for the metal NC community in the future.

Dark septate endophytes (DSEs) can form reciprocal symbioses with most terrestrial plants, providing them with mineral nutrients in exchange for photosynthetic products. Although the mechanism of plant-DSEs is well understood at the transcriptional level, little is known about their post-transcriptional regulation, and microRNAs (miRNAs) for the symbiotic process of DSE infestation of raspberry have not been identified. In this study, we comprehensively identified the miRNAs of DSE-infested raspberry symbiosis using Illumina sequencing. A total of 361 known miRNAs and 95 novel miRNAs were identified in the roots. Similar to other dicotyledons, most of the identified raspberry miRNAs were 21 nt in length. Thirty-seven miRNAs were differentially expressed during colonization after inoculation with Phialocephala fortinii F5, suggesting a possible role for these miRNAs in the symbiotic process. Notably, two miRNAs (miR171h and miR396) previously reported to be responsive to symbiotic processes in alfalfa also had altered expression during raspberry symbiosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggests that miRNAs are mainly involved in regulatory mechanisms, such as biological processes, cellular metabolic processes, biosynthesis of secondary metabolites, plant-pathogen interactions, and phytohormone signaling pathways. This study revealed the potential conservation of miRNA-mediated post-transcriptional regulation in symbiotic processes among plants and provides some novel miRNAs for understanding the regulatory mechanisms of DSE-raspberry symbiosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Yuan, Zhu, Jiang, Yang and Li.)

Sludge incineration is one of the most efficient sludge treatment methods. The fly ash produced by incineration must be handled further since it has a significant number of heavy metals. In this study, the chemical composition of sewage sludge incineration fly ash (SSA) generated from Zhejiang in various months was identified by XRD, X-ray fluorescence spectrometer (XRF), and SEM analyzes. The SSA were treated by a (NH 4 ) 2 SO 4 roasting-acid leaching process to determine its effect on the elimination performance of heavy metals. The SSA content on the mechanical properties and heavy metal leaching of modified SSA-filled PP composite were also studied. Results show (NH 4 ) 2 SO 4 roasting-acid leaching process has a good effect of eliminating heavy metals, with the highest leaching of Zn of 86.4%. The presence of sodium stearate modifier increases activation index of SSA and then improves the compatibility of SSA particles in PP, resulting for the composites have relatively excellent mechanical properties. For the toxicity characteristic leaching procedure (TCLP) test, modified SSA particles can be effectively encapsulated with PP resins, which have a considerable inhibitory effect on heavy metal leaching. This process from this study provides a reference for sewage sludge treatment by using modified SSA as a polymer filler to achieve the immobilization of heavy metals and the resource recycling., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Calmodulin-like proteins (CMLs) are calcium (Ca2+) sensors involved in plant growth and development as well as adaptation to environmental stresses; however, their roles in plant responses to cold are not well understood. To reveal the role of MsCML10 from alfalfa (Medicago sativa) in regulating cold tolerance, we examined transgenic alfalfa and Medicago truncatula overexpressing MsCML10, MsCML10-RNAi alfalfa, and a M. truncatula cml10-1 mutant and identified MsCML10-interacting proteins. MsCML10 and MtCML10 transcripts were induced by cold treatment. Upregulation or downregulation of MsCML10 resulted in increased or decreased cold tolerance, respectively, while cml10-1 showed decreased cold tolerance that was complemented by expressing MsCML10, suggesting that MsCML10 regulates cold tolerance. MsCML10 interacted with glutathione S-transferase (MsGSTU8) and fructose 1,6-biphosphate aldolase (MsFBA6), and the interaction depended on the presence of Ca2+. The altered activities of Glutathione S-transferase and FBA and levels of ROS and sugars were associated with MsCML10 transcript levels. We propose that MsCML10 decodes the cold-induced Ca2+ signal and regulates cold tolerance through activating MsGSTU8 and MsFBA6, leading to improved maintenance of ROS homeostasis and increased accumulation of sugars for osmoregulation, respectively., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A novel co-catalyst system under visible-light irradiation was constructed using high-purity metal and alloy mesh and a Mn 0.5 Cd 0.5 S photocatalyst with a narrow band gap (1.91 eV) prepared by hydrothermal synthesis. The hydrogen production rate of Mn 0.5 Cd 0.5 S changed from 2.21 to 6.63 mmol·(g·h) -1 with the amount of thioacetamide, which was used as the sulphur source. The introduction of Ag, Mo, Ni, Cu, and Cu-Ni alloy meshes efficiently improved the H 2 production rate of the co-catalyst system, especially for the Ni mesh. The improvement can reach an approximately six times greater production, with the highest H 2 production rate being 37.65 mmol·(g·h) -1 . The results showed that some bulk non-noble metal meshes can act as good or better than some noble metal nanoparticles deposited on the main photocatalyst for H 2 evolution due to the promotion of photoinduced electron transfer, increase in redox reaction sites, and prevention of the recombination of carriers.

Melanoma cells display distinct intrinsic phenotypic states. Here, we seek to characterize the molecular regulation of these states using multi-omic analyses of whole exome, transcriptome, microRNA, long non-coding RNA and DNA methylation data together with reverse-phase protein array data on a panel of 68 highly annotated early passage melanoma cell lines. We demonstrate that clearly defined cancer cell intrinsic transcriptomic programs are maintained in melanoma cells ex vivo and remain highly conserved within melanoma tumors, are associated with distinct immune features within tumors, and differentially correlate with checkpoint inhibitor and adoptive T cell therapy efficacy. Through integrative analyses we demonstrate highly complex multi-omic regulation of melanoma cell intrinsic programs that provide key insights into the molecular maintenance of phenotypic states. These findings have implications for cancer biology and the identification of new therapeutic strategies. Further, these deeply characterized cell lines will serve as an invaluable resource for future research in the field., (© 2022. The Author(s).)

Salinity is a major limiting factor that affects crop production. Understanding of the mechanisms of plant salt tolerance is critical for improving crop yield on saline land. Alfalfa ( Medicago sativa L.) is the most important forage crop, while its salt tolerance mechanisms are largely unknown. The physiological and transcriptomic responses in two contrasting salt tolerant cultivars to salinity stress were investigated in the present study. "Magnum Salt" showed higher salt tolerance than "Adrenalin," with higher relative germination rate, survival rate, biomass and K + /Na + ratio after salt treatment. Activities of antioxidant enzymes SOD, CAT and GR, and proline concentrations were upregulated to higher levels in roots and shoots in Magnum Salt than in Adrenalin after salinity stress, except for no difference in GR activity in shoots, and lower levels of O 2 ⋅- and H 2 O 2 were accumulated in leaves. It was interesting to find that salinity caused a decrease in total unsaturated fatty acid in Adrenalin other than Magnum Salt, C18:2 was increased significantly after salinity in Magnum Salt, while it was unaltered in Adrenalin. High quality RNA sequencing (RNA-seq) data was obtained from samples of Magnum Salt and Adrenalin at different time points (0, 2, and 26 h). Generally, "phagosome," "TCA cycle" and "oxidative phosphorylation" pathways were inhibited by salinity stress. Upregulated DEGs in Magnum Salt were specifically enriched in "fatty acid metabolism," "MAPK signaling" and "hormone signal transduction" pathways. The DEGs involved in ionic homeostasis, reactive oxygen species (ROS) scavenging and fatty acid metabolism could partially explain the difference in salt tolerance between two cultivars. It is suggested that salt tolerance in alfalfa is associated with regulation of ionic homeostasis, antioxidative enzymes and fatty acid metabolism at both transcriptional and physiological level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Ma, Sun, Lu, Shi, Guo and Zhu.)

Treatment with therapy targeting BRAF and MEK (BRAF/MEK) has revolutionized care in melanoma and other cancers; however, therapeutic resistance is common and innovative treatment strategies are needed 1,2 . Here we studied a group of patients with melanoma who were treated with neoadjuvant BRAF/MEK-targeted therapy ( NCT02231775 , n = 51) and observed significantly higher rates of major pathological response (MPR; ≤10% viable tumour at resection) and improved recurrence-free survival (RFS) in female versus male patients (MPR, 66% versus 14%, P = 0.001; RFS, 64% versus 32% at 2 years, P = 0.021). The findings were validated in several additional cohorts 2-4 of patients with unresectable metastatic melanoma who were treated with BRAF- and/or MEK-targeted therapy (n = 664 patients in total), demonstrating improved progression-free survival and overall survival in female versus male patients in several of these studies. Studies in preclinical models demonstrated significantly impaired anti-tumour activity in male versus female mice after BRAF/MEK-targeted therapy (P = 0.006), with significantly higher expression of the androgen receptor in tumours of male and female BRAF/MEK-treated mice versus the control (P = 0.0006 and P = 0.0025). Pharmacological inhibition of androgen receptor signalling improved responses to BRAF/MEK-targeted therapy in male and female mice (P = 0.018 and P = 0.003), whereas induction of androgen receptor signalling (through testosterone administration) was associated with a significantly impaired response to BRAF/MEK-targeted therapy in male and female patients (P = 0.021 and P < 0.0001). Together, these results have important implications for therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To characterize a novel HLA allele, A*24:191, its DNA sequence, MHC modeling structure, and the possible influence of the amino-acid residue variations on the molecule., Methods: The HLA sequence was determined by Luminex PCR-SSO and PCR-SBT. Its MHC molecular structure and the possible effects of the amino-acid residue variations were modeled and analyzed with Phyre2, RCSB PDB and HistoCheck software., Results: The PCR-SBT revealed the novel A*24:191 differs from A*24:02 in exon 2 at position 256, 265, 270 with G>C, G>C, A>T. The MHC molecular structure prediction showed that, compared with A*24:02, the 62nd residue of A*24:191 changed from the acidic E to a neutral Q, both with the side chain extending outside the α helix pointing forward the groove, (Risler's score, R=2), the 65th changed from the smaller neutral G extending inside the helix to a basic R with a long-chain extending upward outside the helix (R=52), and the 66th changed from the basic K to a neutral N both with a long side chain extending inside the groove (R=31). The above residues are located on the α helix of the α 1 domain which constituting the side wall of the peptide-binding groove. The DSS Score=3.85. From the surface image of the molecule, it can be clearly seen that the variations of the properties, sizes and configurations of the residues caused significant changes in the shape of the surface structure of the α helix., Conclusion: It suggested that the residue variations are likely to change the peptide binding properties as well as the TCR and antibody binding characteristics of the molecule.

Glacier collapse is a fairly new type of glacier-related disasters on the Asian Water Towers (AWTs) in the warming climate. On 16 October and 29 October 2018, two glacier collapses occurred in the Sedongpu Basin, 7 km downstream from Gyala Village, Paizhen Town, Miling County, on the Yarlung Tsangpo River (YTR). The ice and entrained debris flows caused by the glacier collapses blocked the YTR, resulting in a potential threat to residents and transport lines upstream and downstream. Through post-event field investigations with a helicopter and an unmanned aerial vehicle (UAV), remote sensing interpretation, and seismic, hydrological, and meteorological observations, the process and potential mechanisms of the glacier collapse-induced river blocking (GCRB) disasters were investigated. We confirmed that the first glacier collapse event occurred at 22:48 (Beijing time) on 16 October 2018 and the second began at 08:03 on 29 October 2018. Approximately 130 × 10 6  m 3 of ice and debris detached from the glacier during the glacier collapse, and we calculated that the river blocking fans caused by the first and second glacier collapse event covered ~1.36 km 2 and ~ 1.29 km 2 on the main watercourse of the YTR, respectively. We determined that the GCRB incidents represent a disaster chain of glacier collapse → glacial debris flow → river blockage → dammed lake → outburst flood. These incidents arise due to a combination of factors, including glacier activity, climate warming, heavy precipitation, pre-seismic activity, and high topographic relief. In the context of climate warming on the Tibetan Plateau, such glacier collapse induced disaster chains will continue or even intensify in the future. To protect against glacier collapse disasters in the Grand Canyon on the YTR, we established a monitoring and early warning system (EWS), which has already successfully sounded alerts for GCRB incidents. As a major element of an integrated risk management strategy, the EWS represents a viable and promising tool for mitigating climate change-related risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Methicillin-resistant Staphylococcus aureus (MRSA) is considered as one of the most dangerous clinical pathogens. Biofilms forming ability of MRSA is also a major cause of drug resistance. Hence, it is in urgent need to develop novel antibacterial/antibiofilm drugs. Fascaplysin with a unique cationic five-ring coplanar backbone is emerging as a potential antibacterial compound. In this study, aiming at developing novel and more effective agents, a series of fascaplysin derivatives and their corresponding β-carboline precursors have been synthesized. Then their antibacterial/antibiofilm activity and mechanisms against MRSA were investigated for the first time. The results showed that most fascaplysins rather than β-carboline precursors exhibit superior antimicrobial activity against MRSA ATCC43300, demonstrating the important role of cationic five-ring coplanar backbone playing in antibacterial activity. Among them, 14 and 18 are the most potent compounds with MIC value of 0.098 μg/ml (10-fold lower than vancomycin), and 18 featuring the lowest toxicity. Subsequent mechanisms exploration indicates that 18 has relatively stronger ability to destroy bacterial cell wall and membrane, higher binding affinity to bacterial genomic DNA. Molecular docking study revealed that besides the key role of cationic five-ring coplanar backbone, introduction of N-aryl amide at 9-position of fascaplysin promoted the combination of compound 18 and DNA via additional π-π stacking and hydrogen bonding of the naphthyl group. Moreover, fascaplysins could inhibit MRSA biofilm formation in vitro and bacterial infection in vivo. All these results illustrate that fascaplysin derivative 18 is a strong and safe multi-target antibacterial agent, which makes it an attractive candidate for the treatment of MRSA and its biofilm infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Root-knot nematodes (RKNs) are devastating parasites that invade thousands of plants. In this study, five RKN effectors, which might interact with Prunus sogdiana resistance protein PsoRPM3, were screened and identified. In situ hybridisation results showed that MiCal, MiGST&#95;N&#95;4, MiEFh and MiACPS are expressed in the subventral oesophageal glands (SvG), and MiTSPc hybridization signals are found in the dorsal esophageal gland (DG) of Meloidogyne incognita in the pre-J2. RT-qPCR data indicated that the expression of MiCal , MiGST&#95;N&#95;4 , MiEFh , and MiACPS genes are highly expressed in M. incognita of pra-J2 and J3/J4 stages. The expression of MiTSPc increased significantly in the female stage of M. incognita . Moreover, all effectors found in this study localize in the cytoplasm and nucleus when transiently expressed in plant cells. In addition, MiGST&#95;N&#95;4, MiEFh, MiACPS and MiTSPc can elicit the ROS burst and strong hypersensitive response (HR), as well as significant ion leakage. Our data suggest that MiGST&#95;N&#95;4, MiEFh, MiACPS and MiTSPc effectors may be involved in triggering the immune response of the host plant.

Background: Our goal was to compare the metabolic curves of plasma clearance of iohexol (Cl IOH ) at standard dose (5 ml) and contrast-level dose (50 ml)., Methods: The concentration of iohexol was measured at fasting state and at nine different time periods after a single bolus of iohexol injection. The interval between the injection of the two doses was longer than 24 hrs. Using a multi-point method and a dual-sample method, Cl IOH-M and Cl IOH-D were calculated, and the correlation and consistency of Cl IOH between the two doses were compared., Results: The metabolic curves of iohexol at the 5 ml and 50 ml injection were substantially identical. The correlation of Cl IOH-M between the two doses was 0.930, the mean deviation was 1.3 ± 6.9 ml/min/1.73 m 2 . Taking Cl IOH-5ml-M as the standard, the Cl IOH-50ml-D at 2 h and 4 h had a correlation coefficient of 0.975, a mean deviation of 0.1 ± 5.3 ml/min/1.73 m 2 , and the concordances were 100% corresponding to P 30 , 88.9% corresponding to P 10 , and 77.8% corresponding to P 5 ., Conclusion: When a regular dose of iohexol is used for enhanced CT, Cl IOH can be used for the measurement of GFR, and a proper time for blood collection can be 2 h and 4 h., (Copyright © 2021. Published by Elsevier B.V.)

[Purpose] This study aimed to observe the changes in the thickness of the transverse abdominis muscle after long-term training with a new device using ultrasound imaging and to determine the impact of these changes on chronic low back pain (CLBP). [Participants and Methods] This study included 60 participants with CLBP, who were divided into groups that adopted different positions during the training regimen: new device intervention group (NDG), sitting training group (STG), and supine training group (SPTG). Patients in the NDG used the new device during training. We measured the thickness of the transverse abdominis muscle and determined the pain level using the visual analog scale (VAS). [Results] After 8 weeks of training, the thickness of the transverse abdominis muscle changed in all the three groups, with the change being significantly greater in the NDG than in the other groups. Additionally, the VAS results indicated that the pain relief was highest when the new device was used. [Conclusion] The thickness of the transverse abdominis muscle increased the most in patients who were trained with the new interventional device, and the CLBP was significantly relieved in them., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

[Purpose] This study aimed to observe the thickness of the transverse abdominis muscle in different contraction states using ultrasound, and to investigate the diagnostic capability of transverse abdominal muscle thickness for nonspecific lower back pain. [Participants and Methods] This study included 108 healthy adults (30-50 years old), consisting of 33 participants with low back pain (13 males, 20 females; defined as those who had experienced low back pain for more than six months) and 75 participants without low back pain (22 males, 53 females). The body mass index, body trunk muscle mass, and transverse abdominal muscle thickness, measured at a static state, during the end of inspiration, end of expiration, transverse abdominis contraction, and simultaneous pelvic floor and transverse abdominis muscle contraction, were measured. [Results] Chronic low back pain was correlated with the transverse abdominis muscle thickness during simultaneous transverse abdominis and pelvic floor muscle contraction. [Conclusion] The thickness of the transverse abdominis muscle during simultaneous transverse abdominis and pelvic floor muscle contraction was a viable diagnostic index for evaluating the degree of chronic lower back pain., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Calmodulin-like proteins (CMLs) are one of the Ca 2+ sensors in plants, but the functions of most CMLs remain unknown. The regulation of cold tolerance and flowering time by MtCML42 in Medicago truncatula and the underlying mechanisms were investigated using MtCML42-overexpressing plants and cml42 Medicago mutants with a Tnt1 retrotransposon insertion. Compared with the wild type (WT), MtCML42-overexpressing lines had increased cold tolerance, whereas cml42 mutants showed decreased cold tolerance. The impaired cold tolerance in cml42 could b complemented by MtCML42 expression. The transcript levels of MtCBF1, MtCBF4, MtCOR413, MtCAS15, MtLTI6A, MtGolS1 and MtGolS2 and the concentrations of raffinose and sucrose were increased in response to cold treatment, whereas higher levels were observed in MtCML42-overexpressing lines and lower levels were observed in cml42 mutants. In addition, early flowering with upregulated MtFTa1 and downregulated MtABI5 transcripts was observed in MtCML42-overexpressing lines, whereas delayed flowering with downregulated MtFTa1 and upregulated MtABI5 was observed in cml42. MtABI5 expression could complement the flowering phenotype in the Arabidopsis mutant abi5. Our results suggest that MtCML42 positively regulates MtCBF1 and MtCBF4 expression, which in turn upregulates the expression of some COR genes, MtGolS1 and MtGolS2, which leads to raffinose accumulation and increased cold tolerance. MtCML42 regulates flowering time through sequentially downregulating MtABI5 and upregulating MtFTa1 expression., (© 2021 Society for Experimental Biology and John Wiley & Sons Ltd.)

Key Messages: We reported an NBS-LRR gene, PsoRPM3, is highly expressed following RKN infection, initiating an HR response that promotes plant resistance. Meloidogyne spp. are root-knot nematodes (RKNs) that cause substantial economic losses worldwide. Screening for resistant tree resources and identifying plant resistance genes is currently the most effective way to prevent RKN infestations. Here, we cloned a novel TIR-NB-LRR-type resistance gene, PsoRPM3, from Xinjiang wild myrobalan plum (Prunus sogdiana Vassilcz.) and demonstrated that its protein product localized to the nucleus. In response to Meloidogyne incognita infection, PsoRPM3 gene expression levels were significantly higher in resistant myrobalan plum plants compared to susceptible plants. We investigated this difference, discovering that the - 309 to - 19 bp region of the susceptible PsoRPM3 promoter was highly methylated. Indeed, heterologous expression of PsoRPM3 significantly enhanced the resistance of susceptible tobacco plants to M. incognita. Moreover, transient expression of PsoRPM3 induced a hypersensitive response in tobacco, whereas RNAi-mediated silencing of PsoRPM3 in transgenic tobacco reduced this hypersensitive response. Several hypersensitive response marker genes were considerably up-regulated in resistant myrobalan plum plants when compared with susceptible counterparts inoculated with M. incognita. PsoPR1a (a SA marker gene), PsoPR2 (a JA marker gene), and PsoACS6 (an ET signaling marker gene) were all more highly expressed in resistant than in susceptible plants. Together, these results support a model in which PsoRPM3 is highly expressed following RKN infection, initiating an HR response that promotes plant resistance through activated salicylic acid, jasmonic acid, and ethylene signaling pathways., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims    To systematically review and meta-analyze the impact of aquatic exercise (AE) on cardiovascular health in patients with type 2 diabetes mellitus (T2DM).Material and methods    Relevant literature about AE in patients with T2DM up to May 25, 2021, were collected from the PubMed, the Cochrane, EMBASE, Web of Science, and Ovid databases. The main outcomes were 6‑min walking distance (6MWD) and maximal oxygen uptake (VO2max). Secondary outcomes were resting heart rate (RHR) and resting systolic (RSBP) and diastolic blood pressures (RDBP).Results    12 articles including 320 participants were identified. Among them, three trials compared AE to land-based exercise (LE), six compared AE to non-intervention control (Ctrl), and three were pre- / post-AE design without a control group. Meta-analysis showed that compared with baseline, VO2max increased (WMD=0.71, 95 %CI 0.47 to 0.94), while RHR, RSBP and RDBP declined (WMD=-5.88, 95 %CI -6.88 to -4.88; WMD=-5.76, 95 %CI -7.75 to -3.78; WMD= -2.48, 95 %CI -3.83 to -1.13, respectively) post-AE. 6WMD and VO2max increased (WMD=127.00, 95 %CI 49.26 to 204.74; WMD=2.02, 95 %CI 1.66 to 2.38, respectively) and RHR declined (WMD=-4.20, 95 %CI -6.36 to -2.03, AE vs Ctrl) when AE was compared to Ctrl. There were no significant differences in the above indicators between AE and LE.Conclusions    AE, like LE, increases VO2max, and reduces RHR, RSBP, and RDBP. These responses may improve cardiovascular health in patients with T2DM. However, more data are needed to confirm the effect of AE on 6MWD in T2DM patients.

Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system (siSTING@HP gel ) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the siSTING@HP gel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery., (© 2021 The Authors.)

The root-knot nematode ( Meloidogyne incognita ) causes huge economic losses in the agricultural industry throughout the world. Control methods against these polyphagous plant endoparasites are sparse, the preferred one being the deployment of plant cultivars or rootstocks bearing resistance genes against Meloidogyne species. Our previous study has cloned one resistance gene, PsoRPM3 , from Xinjiang wild myrobalan plum ( Prunus sogdiana ). However, the function of PsoRPM3 remains elusive. In the present study, we have investigated the regulatory mechanism of PsoRPM3 in plant defense responses to M. incognita . Our results indicate that fewer giant cells were detected in the roots of the PsoRPM3 transgenic tobacco than wild tobacco lines after incubation with M. incognita . Transient transformations of full-length and TN structural domains of PsoRPM3 have induced significant hypersensitive responses (HR), suggesting that TIR domain might be the one which caused HR. Further, yeast two-hybrid results revealed that the full-length and LRR domain of PsoRPM3 could interact with the transcription factor Pso9TF . The addition of Pso9TF increased the ROS levels and induced HR. Thus, our data revealed that the LRR structural domain of PsoRPM3 may be associated with signal transduction. Moreover, we did not find any relative inductions of defense-related genes PsoEDS1 , PsoPAD4 and PsoSAG101 in P. sogdiana , which has been incubated with M. incognita . In summary, our work has shown the key functional domain of PsoRPM3 in the regulation of defense responses to M. incognita in P. sogdiana .

Limited studies have been carried out on the historical variations of atmospheric polycyclic aromatic hydrocarbons (PAHs), especially in remote regions of the world. In this study, century-long record of PAHs (1916-2018) were reconstructed from tree rings in the remote southeastern Tibetan Plateau (TP). The total concentrations of 15 PAHs varied from 27.5 to 6.05 × 10 2 ng/g dry weight (dw), with a mean value of 1.40 × 10 2 ng/g dw. Higher levels of PAHs were observed during World War Ⅱ and the Peaceful Liberation of Tibet, and increasing trends were observed starting from rapid industrialization in India. Both the isomer ratios and the positive matrix factorization model results indicated biomass and coal combustion were the dominant sources of PAHs. The carcinogenic risk of PAHs to local residents was assessed, which might have been negligible in most past periods and lower than in other regions of the world. Nevertheless, since the beginning of the 21st century, the cancer risk has been increasing year by year, indicating more actions are needed to reduce emissions of PAHs. This study provides an idea for reconstructing the pollution history of PAHs at the global scale., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A number of studies indicate that circular RNAs (circRNAs) play paramount roles in regulating the biological behavior of glioblastoma multiforme (GBM). In this study, we investigated the underlying mechanism of circMELK in GBM. Real-time PCRs were used to examine the expression of circMELK in glioma tissues and normal brain tissues (NBTs). Localization of circMELK in GBM cells was estimated by fluorescence in situ hybridization (FISH). Transwell migration and three-dimensional invasion assays were performed to examine glioma cell migration and invasion in vitro . Spheroid formation, clonogenicity, and cell viability assays were implemented to test the stemness of glioma stem cells (GSCs). The functions of circMELK in vivo were investigated in a xenograft nude-mouse model. We have proved that circMELK functions as a sponge for tumor suppressor microRNA-593 (miR-593) by RNA immunoprecipitation and circRNA precipitation assays, which targets the oncogenic gene Eph receptor B2 (EphB2). Dual-luciferase reporter assays were adopted to estimate the interactions between miR-593 and circMELK or EphB2. We demonstrated that circMELK was upregulated in GBM, acting as an oncogene and regulating GBM mesenchymal transition and GSC maintenance via sponging of miR-593. Furthermore, we found that EphB2 was involved in circMELK/miR-593 axis-induced GBM tumorigenesis. This function opens the opportunity for the development of a novel therapeutic target for the treatment of gliomas., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: Our aim was to investigate the association between XbaI gene polymorphisms in the apolipoprotein B (APOB) gene and gallstone disease (GD) risk through a comparison of the allele and genotype distribution frequencies at this site using meta-analysis., Methods: A literature search was performed using PubMed and Wanfang through Jun 1, 2020. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of associations., Results: After a comprehensive search, 14 different articles that met the inclusion criteria were selected, with 1583 cases and 1794 controls. Individuals carrying the A-allele or AA genotype of the rs693 polymorphism were determined to possibly have an increased risk of GD. For example, there was a significant relationship between the rs693 polymorphism and increased GD risk in the whole group (OR: 1.40, 95 % CI: 1.05-1.87 in the allelic contrast model), the Asian population (OR: 1.58, 95 % CI: 1.48-2.84 in the heterozygote model), and the hospital-based source of the control (OR: 1.79, 95 % CI: 1.13-2.84 in the dominant model)., Conclusions: This study suggests that the APOB rs693 polymorphism is potentially associated with GD susceptibility, which might offer a detection marker for use in future large scale clinic research.

Purpose: Osteoarthritis (OA) is a multifactorial joint disease and inflammatory processes contribute to joint destruction. Isovitexin (IVX) is a flavone component found in passion flower, Cannabis and, and the palm that is known for its anti-inflammatory properties., Materials and Methods: This study investigated in vitro the role and underlying mechanism used by IVX in its regulation of OA development. Effects of IVX on the viability of chondrocytes were measured by CCK-8 assays. The phenotypes of extracellular matrix (ECM) degeneration and inflammation were measured by qPCR, Western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and Western blot. Molecular docking was applied to predict the interacting protein of IVX, while Nrf2 was knocked down by siRNAs to confirm its role., Results: We demonstrated that IVX suppressed ECM degeneration and suppressed pro-inflammatory factors in IL-1β-treated chondrocytes. Additionally, IVX impact on NF-κB signaling in IL-1β-exposed chondrocytic cells; Mechanistically, it was also demonstrated in molecular docking and knock down studies that IVX might bind to Nrf2 to suppress NF-κB pathway., Conclusion: Our data suggest that IVX halts OA disease advancement through the Nrf2/NF-κB axis, suggesting a possibility of IVX as a target for OA therapy., Competing Interests: The authors have no conflicts of interest., (© 2021 Hu et al.)

For some horticultural plants, auxins can not only induce normal fruit setting but also form fake seeds in the induced fruits. This phenomenon is relatively rare, and, so far, the underlying mechanism remains unclear. In this study, "Fenghou" ( Vitis vinifera × V. labrusca ) grapes were artificially emasculated before flowering and then sprayed with 4-CPA (4-chlorophenoxyacetic acid) to analyze its effect on seed formation. The results show that 4-CPA can induce normal fruit setting in "Fenghou" grapes. Although more seeds were detected in the fruits of the 4-CPA-treated grapevine, most seeds were immature. There was no significant difference in the seed shape; namely, both fruit seeds of the grapevines with and without 4-CPA treatment contained a hard seed coat. However, the immature seeds lacked embryo and endosperm tissue and could not germinate successfully; these were considered defective seeds. Tissue structure observation of defective seeds revealed that a lot of tissue redifferentiation occurred at the top of the ovule, which increased the number of cell layers of the outer integument; some even differentiated into new ovule primordia. The qRT-PCR results demonstrated that 4-CPA application regulated the expression of the genes VvARF2 and VvAP2 , which are associated with integument development in "Fenghou" grape ovules. Together, this study evokes the regulatory role of 4-CPA in the division and continuous redifferentiation of integument cells, which eventually develop into defective seeds with thick seed coats in grapes.

Glioblastoma multiforme (GBM) is the most malignant form of the brain tumors. EGFR variant III (EGFRvIII) is expressed in about 30% of GBM specimens, but not expressed in normal brain tissues. Therefore, EGFRvIII protein offers an ideal CAR-T therapeutic target for EGFRvIII-positive GBM patients. PD-L1 is expressed in a variety of cancer cells, including GBM. Tumor-associated PD-L1 can bind to PD-1 on T cells and promote apoptosis of T cells, thus suppressing the anti-cancer immune response. In our current studies, PD-1 WT EGFRvIII-CAR-T cells and PD-1 KD EGFRvIII-CAR-T cells were generated. Cytokine production and lytic activity of these two CAR-T cells against to PD-L1 WT EGFRvIII + U373 cells or PD-L1 KO EGFRvIII + U373 cells were evaluated. The results showed that PD-1 KD EGFRvIII-CAR-T cells and PD-1 WT EGFRvIII-CAR-T cells showed same levels of interferon-γ (IFN-γ) and interleukin-2 (IL-2) production as well as cytolytic activity against PD-L1 KO EGFRvIII + U373 cells; however, PD-1 KD EGFRvIII-CAR-T cells exhibited higher levels of IFN-γ and IL-2 production as well as cytolytic activity against PD-L1 + EGFRvIII + U373 cells than that of PD-1 WT EGFRvIII-CAR-T cells. PD-1 KD EGFRvIII-CAR-T cells also exhibited higher anti-glioma activity and longer survival in mice in vivo than that of PD-1 WT EGFRvIII-CAR-T cells. Taken together, our findings indicate that PD-1 knockout enhances lytic activity of EGFRvIII-CAR-T cells against PD-L1 + EGFRvIII + GBM cells. These might provide a new insight into strategy of GBM CAR-T cell therapy.

Introduction: Hodgkin lymphoma (HL) is a type of lymphoma common throughout the western countries. However, the detailed mechanisms and special biomarkers of HL remain to be further investigated. Emerging studies have shown that long non-coding RNAs play a key role in human cancers., Material and Methods: In the present work, we constructed relapse-related lncRNA-mediated ceRNA networks in HL. Additionally, we constructed co-expression networks for these relapse-related lncRNAs. We also constructed a relapse-related lncRNA-miRNA-mRNA network to study the potential mechanism of these lncRNAs. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore functions of DEGs in Hodgkin lymphoma., Results: A total of 18 lncRNAs were found to be dysregulated between early relapse and late relapse HL. Six lncRNAs (PCBP1-AS1, HCG18, GAS5, PSMD6-AS2, PRKCQ-AS1, SNHG6), 116 mRNAs and 121 miRNAs were included in the ceRNA network. Bioinformatics analyses revealed that these lncRNAs were significantly involved in regulating immune system processes, responses to chemical stimuli and responses to stress. Among them, HCG18 and PCBP1-AS1 were identified as key lncRNAs in HL relapse., Conclusions: Our results for the first time constructed the key relapse-related lncRNA-mediated ceRNA networks in Hodgkin lymphoma progression. We trust that this work will provide a new therapeutic and prognostic target for HL., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia & Banach.)