Regulation of nitrogen utilization and mycotoxin biosynthesis by the GATA transcription factor AaAreA in Alternaria alternata.

Alternaria alternata is a prevalent postharvest pathogen that generates diverse mycotoxins, notably alternariol (AOH) and alternariol monomethyl ether (AME), which are recurrent severe contaminants. Nitrogen sources modulate fungal growth, development, and secondary metabolism, including mycotoxin production. The GATA transcription factor AreA regulates nitrogen source utilization. However, little is known about its involvement in the regulation of nitrogen utilization in A. alternata. To examine the regulatory mechanism of AaAreA on AOH and AME biosynthesis in A. alternata, we analyzed the impact of diverse nitrogen sources on the fungal growth, conidiation and mycotoxin production. The use of a secondary nitrogen source (NaNO3) enhanced mycelial elongation and sporulation more than the use of a primary source (NH4Cl). NaNO3 favored greater mycotoxin accumulation than did NH4Cl. The regulatory roles of AaAreA were further clarified through gene knockout. The absence of AaAreA led to an overall reduction in growth in minimal media containing any nitrogen source except NH4Cl. AaAreA positively regulates mycotoxin biosynthesis when both NH4Cl and NaNO3 are used as nitrogen sources. Subcellular localization analysis revealed abundant nuclear transport when NaNO3 was the sole nitrogen source. The regulatory pathway of AaAreA was systematically revealed through comprehensive transcriptomic analyses. The deletion of AaAreA significantly impedes the transcription of mycotoxin biosynthetic genes, including aohR, pksI and omtI. The interaction between AaAreA and aohR, a pathway-specific transcription factor gene, demonstrated that AaAreA binds to the aohR promoter sequence (5'-GGCTATGGAAA-3'), activating its transcription. The expressed AohR regulates the expression of downstream synthase genes in the cluster, ultimately impacting mycotoxin production. This study provides valuable information to further understand how AreA regulates AOH and AME biosynthesis in A. alternata, thereby enabling the effective design of control measures for mycotoxin contamination.

The A-kinase anchoring protein Yotiao decrease the ER calcium content by inhibiting the store operated calcium entry.

The meticulous regulation of ER calcium (Ca2+) homeostasis is indispensable for the proper functioning of numerous cellular processes. Disrupted ER Ca2+ balance is implicated in diverse diseases, underscoring the need for a systematic exploration of its regulatory factors in cells. Our recent genomic-scale screen identified a scaffolding protein A-kinase anchoring protein 9 (AKAP9) as a regulator of ER Ca2+ levels, but the underlying molecular mechanisms remain elusive. Here, we reveal that Yotiao, the smallest splicing variant of AKAP9 decreased ER Ca2+ content in animal cells. Additional testing using a combination of Yotiao truncations, knock-out cells and pharmacological tools revealed that, Yotiao does not require most of its interactors, including type 1 inositol 1,4,5-trisphosphate receptors (IP3R1), protein kinase A (PKA), protein phosphatase 1 (PP1), adenylyl cyclase type 2 (AC2) and so on, to reduce ER Ca2+ levels. However, adenylyl cyclase type 9 (AC9), which is known to increases its cAMP generation upon interaction with Yotiao for the modulation of potassium channels, plays an essential role for Yotiao's ER-Ca2+-lowering effect. Mechanistically, Yotiao may work through AC9 to act on Orai1-C terminus and suppress store operated Ca2+ entry, resulting in reduced ER Ca2+ levels. These findings not only enhance our comprehension of the interplay between Yotiao and AC9 but also contribute to a more intricate understanding of the finely tuned mechanisms governing ER Ca2+ homeostasis.

Oxidation of p-toluenesulfonic acid fractionated hybrid Pennisetum by different methods for carboxylated nanocellulose preparation: The evaluation of efficiency and sustainability.

An innovative two-step process with p-toluenesulfonic acid (p-TsOH) and oxidation treatment was proposed for the efficient preparation of carboxylated nanocellulose from hybrid Pennisetum. Approximately 90 % of lignin was dissolved by p-TsOH acid under the optimal condition (80 °C, 20 min). Near-complete delignification (down to 0.5 %) and introduction of carboxylate groups (up to 1.48 mmol/g) could be achieved simultaneously during cellulose oxidation treatments without the requirement for bleaching. However, different oxidation methods expressed different efficiency and sustainability. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) oxidation has higher selectivity for the carboxylation reaction but with detriment to the aquatic environment. Fenton oxidation is more energy-consuming due to the lower carboxylate contents of products (maximum 188 µmol/g), with the carboxylic groups present as carboxylic acids, but competitive in terms of environmental sustainability, especially when renewable energy sources are available. The nanocelluloses obtained by the two oxidation methods differ in morphology and have different application prospects.

Shift work and menstruation: A meta-analysis study.

Background: Shift work is a potential risk factor for women's reproductive health. Evidence suggests that shift work is associated with menstrual disorders, reproductive disturbances, and adverse pregnancy outcomes. However, previous studies did not systematically examine the results of menstrual irregularities, dysmenorrhea, and early menopause at the same time. Objective: To determine the relationship between shift work and women's menstrual characteristics (e.g., irregular menstruation, dysmenorrhea, and early menopause). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched up to December 2022. The study characteristics and risk assessment values of the literature were extracted from 21 studies that met the criteria. Odds ratios (ORs), relative risks (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated to assess the relationship between shift work exposure and menstruation. The included studies were evaluated for heterogeneity, publication bias, sensitivity analysis, and subgroup analysis. Results: A total of 21 studies with 195,538 female participants, including 16 cross-sectional studies and 5 cohort studies, were included in this meta-analysis. According to the quality evaluation, the included research had high methodological quality. The overall ORs of shift work for the likelihood of irregular menstruation and dysmenorrhea were 1.30 (95% CI, 1.23-1.36) (I2 = 41.9%, P < 0.05) and 1.35 (95% CI, 1.04-1.75) (I2 = 73.0%, P < 0.05), respectively. There was a significant positive association between shift work and the risk of early menopause (HR = 1.09, 95% CI, 1.04-1.14), without significant heterogeneity (I2 = 0.0%, P > 0.05). Conclusions: This meta-analysis indicated that shift workers have significantly higher odds of menstrual disorders, dysmenorrhea, and early menopause. This study focuses on female reproductive health and has broad implications for adjusting optimal working hours and shift schedules for female workers.

Association Between Serum Chemokine Ligand 20 Levels and Disease Activity and Th1/Th2/Th17-Related Cytokine Levels in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a type of arthritis autoimmune disease characterized by systemic chronic inflammation. C-C Chemokine ligand 20 (CCL20) is the same as most chemokines with immunomodulatory and inflammatory processes. The correlation of CCL20 in RA remains unclear. This study aimed to explore the association among levels of CCL20, T helper cell (TH) subset (Th1/Th2/Th17)-related cytokine levels, and clinical indices of RA disease activity. Serum CCL20 levels were quantified by enzyme-linked immunosorbent assay, and a flow-fluorescence technique was used to assess Th1/Th2/Th17-related cytokine levels. The serum CCL20 levels in patients were significantly higher than those in healthy controls and positively associated with C-reactive protein levels, erythrocyte sedimentation rate, and disease activity score-28 (DAS28). Patients with RA were categorized into 4 major groups, including remission, low, moderate, and high disease activity, with related DAS28 scores for each group. CCL20 levels of the disease moderate/high activity group were moderately positively correlated with IL-6 levels, but not with the other Th1/Th2/Th17-related cytokines. Serum CCL20 levels correlate strongly with RA disease activity and clinical inflammation and were significantly elevated in patients compared to healthy individuals. CCL20 plays a key role in the immune response of patients with RA and is, therefore, a potential biomarker of disease activity.

Combined metabolome and transcriptome analysis reveal the mechanism of eugenol inhibition of Aspergillus carbonarius growth in table grapes (Vitis vinifera L.).

During storage, Aspergillus carbonarius (A. carbonarius) can easily infect grape berries, resulting in a pronounced decline in nutritional value and substantial economic loss for the grape industry. Characterised by broad-spectrum antibacterial activity, eugenol is proven to significantly inhibit A. carbonarius and ochratoxin A (OTA) in vitro. In this study, the potential mechanism of eugenol against A. carbonarius in grapes ('Kyoho') was evaluated using integrative transcriptomic and metabolomics analyses. After eugenol treatment at 50 mM, the inhibition of OTA was reduced by 100%, despite a 56.2% inhibition of A. carbonarius. In the meantime, mycelial growth was completely inhibited by 100 mM eugenol in grape berries. The application of eugenol to grapes stimulated the activity of several enzymes involved in disease resistance, namely catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), chitinase (CHI), ß-1,3-glucanase (GLU), cinnamate-4-hydroxylase (C4H), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL) and glutathione (GSH) content. In addition, the contents of abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA) in eugenol-treated grapes were higher after A. carbonarius inoculation. Combined transcriptomic and metabolomic analysis revealed that in phenylpropane biosynthesis, there were a variety of differentially expressed metabolites (DEMs) and differentially expressed genes (DEGs), and the plant hormone signalling pathway changed significantly. Among these, the levels of 47 polyphenol metabolites significantly increased in eugenol-treated grape berries compared to noneugenol-treated berries. Meanwhile, we investigated the transcript levels of 39 genes in 6 phytohormones signalling in response to eugenol-treated grape berries followed by A. carbonarius inoculation. These results suggest that eugenol positively improved the disease resistance of grapes and might be potentially beneficial for the prevention and treatment of A. carbonarius-caused disease.

Identifying 2PHDO as a SOCE inhibitor from Chinese herbal extracts.

BACKGROUND: STIM- and Orai-mediated store operated calcium entry (SOCE) is a ubiquitous Ca2+ signaling process, crucial for the proper function of immune, muscle and neuronal systems. To treat SOCE-related disorder or diseases of these systems, and to mechanistically dissect activation and function of SOCE, specific SOCE inhibitors are needed. However, strategies for developing new SOCE modifiers are still limited.

Methodology: In this study, we identified a novel SOCE inhibitor named 2PHDO from a small pool of Chinese herbal extracts used for treating psoriasis. It could block SOCE and SOCE-mediated NFAT translocation in multiple types of cells with a half inhibitory concentration around 1 µM. At this concentration, 2PHDO was specific for SOCE. Mechanistically, 2PHDO didn't affect the activation of STIM1 or its physical coupling with Orai1. Rather, 2PHDO inhibited SOCE via its actions on Orai1.

Results: 2PHDO may serve as a good template for developing new medicines aiming to treat SOCE related diseases.

Conclusion: Overall, we proved the feasibility of screening and identification of novel SOCE inhibitors from active monomers of Chinese herbal medicine.

Association of serum anti-carbamylated protein antibodies with disease activity and bone loss in rheumatoid arthritis.

BACKGROUND: We investigated the association of serum anti-carbamylated protein (anti-CarP) antibodies with disease activity and bone loss in rheumatoid arthritis (RA). METHODS: The serum anti-CarP antibody concentrations of RA and non-RA patients and healthy controls were determined by enzyme-linked immunosorbent assay (ELISA) and then compared. The diagnostic value of anti-CarP antibodies in RA was determined by the receiver operating characteristic curve. Patients with RA and bone erosions were evaluated using ultrasound examinations. Ultrasonography was performed using a semiquantitative scale. The serum receptor activator of nuclear factor Κ-Β ligand (RANKL) concentrations were measured by ELISA to focus on bone loss. RESULTS: Peripheral serum anti-CarP antibody concentrations in patients with RA were significantly higher than those in patients without RA and in healthy controls and were positively correlated with disease activity. Anti-CarP antibody concentrations were significantly increased in patients with anti-CCP-positive RA. Positive correlation were found between anti-CarP and RANKL. Increased serum anti-CarP antibodies in women with postmenopausal osteoporosis (OP). CONCLUSIONS: Anti-CarP antibodies are associated with RA disease activity and may play an important role in bone loss associated with RA. The concentration of anti-CarP antibodies may be beneficial in the early diagnosis of RA, thus supporting its potential as a novel disease biomarker.

Engineering of NEMO as calcium indicators with large dynamics and high sensitivity.

Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.

Combination of Methotrexate and Leflunomide Is Efficient and Safe for 60 Patients with Rheumatoid Arthritis.

The present work is aimed at exploring the clinical efficacy and safety of methotrexate (MTX) and leflunomide (LEF) combination therapy for rheumatoid arthritis. From June 2019 to June 2021, a total of 120 individuals with rheumatoid arthritis received a diagnosis. Sixty patients each were randomly assigned to the control and observation groups. The observation group received MTX and LEF combo medication while the control group only received MTX treatment. Clinical efficacy, complication incidence, and the alleviation of inflammatory markers, joint pain, and clinical symptoms were compared between the 2 groups. Posttreatment, the observation group had overall response rate of 96.66%, while the control group had 86.67%, with significant differences. Compared with pretreatment, both control and observation group patients showed decreasing trends of IL-1 levels and increasing trends of IL-10 levels posttreatment, with significant differences (P < 0.05). Compared with the control group, patients in the observation group had lower IL-1 and TNF-α levels with significant differences (P < 0.05) and higher levels of IL-10 with significant difference (P < 0.05). In both groups, the pain score and the number of painful joints were much lower than they were prior to treatment. Following treatment, the observation group displayed significantly lower levels of erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein than the control group (P < 0.05). Clinical measures in the observation group were all lower than those in the control group with statistically significant differences (P < 0.05). Moreover, the incidence rate of adverse reactions showed no significant difference between these 2 groups (P > 0.05). In conclusion, the combination therapy of MTX and LEF is efficacious for rheumatic arthritis.

Vitamin E functions by association with a novel binding site on the 67 kDa laminin receptor activating diacylglycerol kinase.

It is generally recognized that the main function of α-tocopherol (αToc), which is the most active form of vitamin E, is its antioxidant effect, while non-antioxidant effects have also been reported. We previously found that αToc ameliorates diabetic nephropathy via diacylglycerol kinase alpha (DGKα) activation in vivo, and the activation was not related to the antioxidant effect. However, the underlying mechanism of how αToc activates DGKα have been enigmatic. We report that the membrane-bound 67 kDa laminin receptor (67LR), which has previously been shown to serve as a receptor for epigallocatechin gallate (EGCG), also contains a novel binding site for vitamin E, and its association with Vitamin E mediates DGKα activation by αToc. We employed hydrogen-deuterium exchange mass spectrometry (HDX/MS) and molecular dynamics (MD) simulations to identify the specific binding site of αToc on the 67LR and discovered the conformation of the specific hydrophobic pocket that accommodates αToc. Also, HDX/MS and MD simulations demonstrated the detailed binding of EGCG to a water-exposed hydrophilic site on 67LR, while in contrast αToc binds to a distinct hydrophobic site. We demonstrated that 67LR triggers an important signaling pathway mediating non-antioxidant effects of αToc, such as DGKα activation. This is the first evidence demonstrating a membrane receptor for αToc and one of the underlying mechanisms of a non-antioxidant function for αToc.

High expression of serine and arginine-rich splicing factor 9 (SRSF9) is associated with hepatocellular carcinoma progression and a poor prognosis.

BACKGROUND: Serine and arginine-rich splicing factor 9 (SRSF9) has been linked to the occurrence and progression of various cancers; however, its effects and mechanism of action hepatocellular carcinoma (HCC) have not been reported. In this study, we used a bioinformatics approach and in vitro assays to evaluate the expression of SRSF9 in HCC, its prognostic value, and its underlying regulatory mechanisms, including analyses of related pathways and the role of methylation. METHODS: Transcriptomic and DNA methylation data for 357 HCC cases and 50 paratumor tissues in The Cancer Genome Atlas database were obtained. Additionally, protein expression data for cell lines and tissue samples were obtained from the Human Protein Atlas. The CMap databased was used to predict candidate drugs targeting SRSF9. Various cell lines were used for in vitro validation. RESULTS: SRSF9 expression was significantly elevated in HCC and was negatively regulated by its methylation site cg06116271. The low expression of SRSF9 and hypermethylation of cg06116271 were both associated with a longer overall survival time. A correlation analysis revealed ten genes that were co-expressed with SRSF9; levels of CDK4, RAN, DENR, RNF34, and ANAPC5 were positively correlated and levels of RBP4, APOC1, MASP2, HP, and HPX were negatively correlated with SRSF9 expression. The knockdown of SRSF9 in vitro inhibited the proliferation and migration of HCC cells and significantly reduced the expression of proteins in the Wnt signaling pathway (DVL2 and ß-catenin) and cell cycle pathway (Cyclin D and Cyclin E). A CMap analysis identified two drugs, camptothecin and apigenin, able to target and inhibit the expression of SRSF9. CONCLUSIONS: This study expands our understanding of the molecular biological functions of SRSF9 and cg06116271 and provides candidate diagnostic and therapeutic targets for HCC.

Increased ATP2A1 Predicts Poor Prognosis in Patients With Colorectal Carcinoma.

Colorectal cancer is one of the most common malignant tumors in the digestive system. Traditional diagnosis and treatment methods have not significantly improved the overall survival of patients. In this study, we explored the value of ATP2A1 as a biomarker in predicting the prognosis of colorectal cancer patients. We used the TCGA database to reveal the relationship between ATP2A1 mRNA level and prognosis, methylation, and immune invasion in colorectal cancer. The results showed that the expression of ATP2A1 was increased in colorectal cancer. The overall survival of patients with high expression of ATP2A1 was significantly lower than patients with low expression of ATP2A1. Cox regression analysis showed that high expression of ATP2A1 was an independent risk factor for poor prognosis in colorectal cancer patients. In addition, we used three datasets to perform a meta-analysis, which further confirmed the reliability of the results. Furthermore, we revealed that ATP2A1 could significantly inhibit the proliferation of colorectal cancer cells by inhibiting the autophagy process and was associated with several immune cells, especially CD8 + T cells. Finally, four small molecule drugs with potential inhibition of ATP2A1 expression were found by CMap analysis. This study demonstrates for the first time that ATP2A1 is a potential pathogenic factor, which may play a significant role in colorectal cancer.

Melatonin Alleviates Hyperglycemia-Induced Cardiomyocyte Apoptosis via Regulation of Long Non-Coding RNA H19/miR-29c/MAPK Axis in Diabetic Cardiomyopathy.

Recent studies revealed that non-coding RNAs (ncRNAs) play a crucial role in pathophysiological processes involved in diabetic cardiomyopathy (DCM) that contribute to heart failure. The present study was designed to further investigate the anti-apoptotic effect of melatonin on cardiomyocytes in diabetic conditions, and to elucidate the potential mechanisms associated with ncRNAs. In animal models, we induced diabetes in SD rats by single intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg) at 18:00 in the evening, after a week of adaptive feeding. Our results indicate that melatonin notably alleviated cardiac dysfunction and cardiomyocyte apoptosis. In the pathological situation, lncRNA H19 level increased, along with a concomitant decrease in miR-29c level. Meanwhile, melatonin significantly downregulated lncRNA H19 and upregulated miR-29c levels. In our in vitro experiments, we treated H9c2 cells with high-concentration glucose medium (33 mM) to simulate the state of diabetes. It was verified that positive modulation of miR-29c and inhibition of lncRNA H19, as well as mitogen-activated protein kinase (MAPK) pathways, distinctly attenuated apoptosis in high-glucose-treated H9c2 cells. A luciferase activity assay was conducted to evaluate the potential target sites of miR-29c on lncRNA H19 and MAPK13. LncRNA H19 silencing significantly downregulated the expression of miR-29c target gene MAPK13 by inducing miR-29c expression. Most importantly, our results show that melatonin alleviated apoptosis by inhibiting lncRNA H19/MAPK and increasing miR-29c level. Our results elucidate a novel protective mechanism of melatonin on diabetic cardiomyocyte apoptosis, which involved the regulation of lncRNA H19/miR-29c and MAPK pathways, providing a promising strategy for preventing DCM in diabetic patients.

The Effect of Thunder-Fire Moxibustion on Lumbar Disc Herniation: Study Protocol for a Randomized Controlled Trial.

Background: Lumbar disc herniation (LDH) is a common disease seen in orthopedics; it is caused by nucleus pulposus herniation. Its clinical manifestations are low back pain, radiating pain of the lower limbs, and cauda equina symptoms that seriously affect patients' quality of life. At present, oral analgesics are commonly used in the treatment of LDH; but they can produce gastrointestinal reactions and other side effects. Thunder-fire moxibustion is a method that is widely used in China to treat pain syndromes. This study aimed to design a randomized controlled trial to explore the effectiveness and safety of thunder-fire moxibustion in the treatment of lumbar disc herniation. Methods: Ninety patients will be enrolled and randomly divided into one of two groups: the thunder-fire moxibustion group and the acetaminophen group. The thunder-fire moxibustion group will be treated with moxa sticks at BL25, GV3, BL23, and GV4; and after 15 min of local whirling moxibustion, the contralateral acupoints will be treated with moxibustion for 15 min. The study period will include two 10-day courses of treatment, for a total study duration of 20 days. The acetaminophen group participants will take one acetaminophen sustained-release tablet twice a day for the duration of the study period. In contrast, the thunder-fire moxibustion group participants will be treated with thunder-fire moxibustion every other day for 30 min. The primary outcome will be the Japanese Orthopedic Association (JOA) score. Visual analog scale (VAS) and Oswestry Disability Index (ODI) will be used as the secondary outcome measures. Adverse events (AEs) will also be recorded. Assessments will be conducted at baseline, the end of the first and second courses of treatment. Discussion: This study will determine whether thunder-fire moxibustion is more effective and safer than acetaminophen in the treatment of patients with LDH. Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000036079.

Roles of AaVeA on Mycotoxin Production via Light in Alternaria alternata.

Alternaria alternata is a principal plant pathogen responsible for the biosynthesis of mycotoxins, including tenuazonic acid (TeA), alternariol (AOH), and alternariol monomethyl ether (AME). The velvet gene VeA is involved in fungal growth, development, and secondary metabolism, including mycotoxin biosynthesis via light regulation. In this study, the detailed regulatory roles of AaVeA in A. alternata with various light sources were investigated from the comparative analyses between the wild type and the gene knockout strains. In fungal growth and conidiation, mycelial extension was independent of light regulation in A. alternata. Red light favored conidiation, but blue light repressed it. The absence of AaVeA caused the marked reduction of hyphae extension and conidiophore formation even though red light could not induce more spores in ΔAaVeA mutant. The differentially expressed genes (DEGs) enriched in hyphal growth and conidiation were drastically transcribed from the comparatively transcriptomic profile between the wild type and ΔAaVeA mutant strains with or without light. In mycotoxin production, TeA biosynthesis seems no obvious effect by light regulation, but AOH and AME formation was significantly stimulated by blue light. Nevertheless, the disruption of AaVeA resulted in a marked decrease in mycotoxin production and the action of the stimulation was lost via blue light for the abundant accumulation of AOH and AME in the ΔAaVeA strain. From DEG expression and further verification by RT-qPCR, the loss of AaVeA caused the discontinuous supply of the substrates for mycotoxin biosynthesis and the drastic decline of biosynthetic gene expression. In addition, pathogenicity depends on AaVeA regulation in tomato infected by A. alternata in vivo. These findings provide a distinct understanding of the roles of AaVeA in fungal growth, development, mycotoxin biosynthesis, and pathogenicity in response to various light sources.

Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.

Deregulated store-operated calcium entry (SOCE) mediated by aberrant STIM1-ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1ß, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1ß, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca2+ signaling. At the molecular level, the 31-residue insertion destabilizes STIM1ß by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1ß depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant-specific tumor-promoting role of STIM1ß that can be potentially targeted for glioblastoma intervention.

Research on Discrete Semantics in Continuous Hand Joint Movement Based on Perception and Expression.

Continuous movements of the hand contain discrete expressions of meaning, forming a variety of semantic gestures. For example, it is generally considered that the bending of the finger includes three semantic states of bending, half bending, and straightening. However, there is still no research on the number of semantic states that can be conveyed by each movement primitive of the hand, especially the interval of each semantic state and the representative movement angle. To clarify these issues, we conducted experiments of perception and expression. Experiments 1 and 2 focused on perceivable semantic levels and boundaries of different motion primitive units from the perspective of visual semantic perception. Experiment 3 verified and optimized the segmentation results obtained above and further determined the typical motion values of each semantic state. Furthermore, in Experiment 4, the empirical application of the above semantic state segmentation was illustrated by using Leap Motion as an example. We ended up with the discrete gesture semantic expression space both in the real world and Leap Motion Digital World, containing the clearly defined number of semantic states of each hand motion primitive unit and boundaries and typical motion angle values of each state. Construction of this quantitative semantic expression will play a role in guiding and advancing research in the fields of gesture coding, gesture recognition, and gesture design.

[Problems and countermeasures in clinical studies on acupuncture and moxibustion in course of developing Guideline for Clinical Practice of Acupuncture and Moxibustion: Insomnia].

To explore the problems and countermeasures existing in acupuncture and moxibustion clinical studies, in the perspective of the key steps of Guideline for Clinical Practice of Acupuncture and Moxibustion: Insomnia. The problems include: confusion of disease names and disunity of diagnostic criteria, inadequate refined clinical problems that need to be addressed, lack of targeted analysis of efficacy evaluation index, lack of adequate research on common acupuncture, difficulty to balance innovation and universality, lack of emphasis on the importance of timing for acupuncture, lack of attention to healthy lifestyles and self-care. We suggests that the disease name and diagnostic criteria should refer to the authoritative standards; the clinical study design should based on the realistic clinical problems; the efficacy evaluation index should based on the clinical needs and be analyzed targetedly; further research on common acupuncture or therapy should be carried out.

Engineering of a bona fide light-operated calcium channel.

The current optogenetic toolkit lacks a robust single-component Ca2+-selective ion channel tailored for remote control of Ca2+ signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca2+ selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca2+ channel (designated LOCa) by inserting a plant-derived photosensory module into the intracellular loop of an engineered ORAI1 channel. LOCa displays biophysical features reminiscent of the ORAI1 channel, which enables precise optical control over Ca2+ signals and hallmark Ca2+-dependent physiological responses. Furthermore, we demonstrate the use of LOCa to modulate aberrant hematopoietic stem cell self-renewal, transcriptional programming, cell suicide, as well as neurodegeneration in a Drosophila model of amyloidosis.