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Tomato fruit quality and nutrient dynamics under water deficit conditions: The influence of an organic fertilizer

Drought adversely affects the growth and performance of plants. By contrast, the application of organic modifiers can improve plant growth by supplying nutrients and water. The influence of foliar application of organic fertilizer under water deficit conditions on growth traits, chemical composition, and fruit quality of tomato (Lycopersicon esculentum Mill., var. Maya) were investigated in greenhouse conditions based on bi-plot and principal component analysis (PCA). Plants which were cultivated in soil under greenhouse conditions were subjected to four levels foliar spraying of Zargreen liquid organic fertilizer, ZLOF (0, 2.5, 5, and 7.5 L 1000−1, shown as Z0, Z2.5, Z5, and Z7.5, respectively), and three levels of soil water, SW (100, 75, and 50% of field capacity (FC), shown W100, W75, and W50, respectively). The results of biplot analysis using the different treatments representing 42.9% and 38.3%, 60.3% and 28.8%, and 63.1% and 22.4% of the variance attributed to the first two principal components (PCs) for the PC1 and PC2, under 100, 75, and 50% FC conditions, respectively. Water deficit induced a reduction of fruit dry, and fresh weights. Application of 2.5, 5, and 7.5 L 1000−1 of the organic fertilizer significantly increased fruit fresh weight by 16, 20, and 22% and fruit dry weight by 13, 20, and 20% as compared to that of control, respectively. Vitamin C content of fruit significantly increased by 16 and 33% when respectively 5 and 7.5 L 1000−1 of the organic fertilizer was foliar sprayed. Besides, fruit iron (Fe), sodium (Na (and potassium (K) concentrations increased with the application of the organic fertilizer at different levels of water deficit. Furthermore, the highest fruit zinc (Zn) concentration was obtained at the highest level of both applied organic fertilizer and water deficit. The best treatments were selected with increased PC1 and decreased PC2 for different water conditions. The W100Z7.5, W75Z7.5, and W50Z5 treatments with the higher PC1 and the lower PC2, also exhibited higher scores for fruit dry weight, and Na and K concentrations under W100; vitamin C, number of fruits, fruit fresh weight, and fruit Fe concentration under W75; citric acid, and fruit Fe, Zn, Na, K, and Cu concentrations under W50 treatment. The addition of the organic fertilizer was effective in enhancing the plant growth traits under water deficit conditions. Therefore, it can be concluded that organic fertilizer addition is an effective management strategy to mitigate the adverse effects of drought and improve the quantity and quality of tomato fruit.

Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study

Abstract Although iron overload is a common feature in myelodysplastic syndromes (MDS), it remains unclear how iron excess is detrimental for disease pathophysiology. Taking advantage of complementary approaches, we analyzed the impact of iron overload and restriction achieved through genetic activation of ferroportin (FPN) via the C326S mutation (FPNC326S) and pharmacologic inhibition (vamifeport) of the iron exporter FPN, respectively, in a MDS mouse model. Although FPNC326S-induced iron overload did not significantly improve the late stages of erythroid maturation, vamifeport-mediated iron restriction ameliorated anemia and red blood cell maturation in MDS mice, through the reduction of oxidative stress and apoptosis in erythroid progenitors. Iron overload aggravated, and restriction alleviated, reactive oxygen species formation, DNA damage, and cell death in hematopoietic stem and progenitor cells (HSPCs), resulting in altered cell survival and quality. Finally, myeloid bias, indicated by expanded bone marrow myeloid progenitors and circulating immature myeloid blasts, was exacerbated by iron excess and attenuated by iron restriction. Overall, vamifeport treatment resulted in improved anemia and significant survival increment in MDS mice. Interestingly, the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared with single treatments and offers additive beneficial effects in MDS. Our results prove, to our knowledge, for the first time in a preclinical model, that iron plays a pathologic role in transfusion-independent MDS. This is likely aggravated by transfusional iron overload, as suggested by observations in the FPNC326SMDS model. Ultimately, the beneficial effects of pharmacologic FPN inhibition uncovers the therapeutic potential of early prevention of iron toxicity in transfusion-independent MDS.

Wireless microwave-to-optical conversion via programmable metasurface without DC supply

Metacognitive function in young adults is impacted by physical activity, diet, and sleep patterns

Our cognitive capacities like working memory and attention are known to systematically vary over time with our physical activity levels, dietary choices, and sleep patterns. However, whether our metacognitive capacities––such as our strategic use and optimization of cognitive resources––show a similar relationship with these key lifestyle factors remains unknown. Here we addressed this question in healthy young adults by examining if physical activity, diet, and sleep patterns were predictive of self-reported metacognitive status. Participants completed a set of validated surveys assessing these lifestyle factors over the past week to month, as well as three measures of metacognition. Using multiple regression and exploratory factor analyses we identified four clusters of metacognitive processes that are sensitive to lifestyle behaviours. Specifically, knowledge of and offline regulation of cognition is linked with physical activity, on-line cognitive regulation is related to diet, and metacognitive worry is associated with sleep behaviours. These findings suggest that lifestyle behaviours do not just affect objective cognitive functioning, but also the meta-level processes we use to monitor our cognitive performance and exert strategic control over our cognitive resources.

Single-cell analysis of the multiple myeloma microenvironment after γ-secretase inhibition and CAR T-cell therapy

Abstract Chimeric antigen receptor (CAR) T cells and bispecific antibodies targeting B-cell maturation antigen (BCMA) have significantly advanced the treatment of relapsed and refractory multiple myeloma. Resistance to BCMA-targeting therapies, nonetheless, remains a significant challenge. BCMA shedding by γ-secretase is a known resistance mechanism, and preclinical studies suggest that inhibition may improve anti-BCMA therapy. Leveraging a phase 1 clinical trial of the γ-secretase inhibitor (GSI), crenigacestat, with anti-BCMA CAR T cells (FCARH143), we used single-nuclei RNA sequencing and assay for transposase-accessible chromatin sequencing to characterize the effects of GSI on the tumor microenvironment. The most significant impacts of GSI involved effects on monocytes, which are known to promote tumor growth. In addition to observing a reduction in the frequency of nonclassical monocytes, we also detected significant changes in gene expression, chromatin accessibility, and inferred cell-cell interactions after exposure to GSI. Although many genes with altered expression are associated with γ-secretase–dependent signaling, such as Notch, other pathways were affected, indicating GSI has far-reaching effects. Finally, we detected monoallelic deletion of the BCMA locus in some patients with prior exposure to anti-BCMA therapy, which significantly correlated with reduced progression-free survival (PFS; median PFS, 57 vs 861 days). GSIs are being explored in combination with the full spectrum of BCMA-targeting agents, and our results reveal widespread effects of GSI on both tumor and immune cell populations, providing insight into mechanisms for enhancing BCMA-directed therapies.

Pulmonary artery denervation by noninvasive stereotactic radiotherapy: a pilot study in swine models of pulmonary hypertension

Development of oats flour and bitter gourd fortified cookies: Effects on physicochemical, antioxidant, antimicrobial, and sensory attributes

The objective of this study was the develop of fortified cookies enriched with oats flour and bitter gourd powder and monitoring the effects of these enrichments on the physicochemical, antioxidant, antimicrobial, and sensory attributes. This study was subjected to four treatments: control (0% oats flour and bitter gourd powder), T1 (10% oats flour), T2 (3% bitter gourd powder), and T3 (7% oats flour and 3% bitter gourd powder). Various physical properties of the cookies, including weight, thickness, diameter, spread ratio, baking loss, pH, and color values (L*, a*, and b*), were measured. Proximate analysis revealed moisture (4.23–4.70%), ash (1.17–1.67%), fat (13.62–15.09%), crude protein (7.02–7.36%), carbohydrate (71.78–72.97%), energy (442.62–452.40 kcal), and crude fiber (8.02–3.33%). Mineral contents included Na (787–754 mg/100g), Ca (873–435 mg/100g), and Zn (66.7–58.8 mg/100g). Additionally, DPPH free radical scavenging activity ranged from 13.14 to 75.51%, while TBARS activity varied from 0.78 to 1.33 mg MDA/kg. T2 cookies exhibited the highest antimicrobial activity, with control cookies showing the lowest. The 5-point hedonic scale indicated that T2 cookies had lower overall acceptability, while T3 cookies were better received. In conclusion, the study suggests that fortified cookies have a more significant impact than regular or control cookies.

Lower-intensity therapy for good-risk B-ALL

Hypoxia-induced conversion of sensory Schwann cells into repair cells is regulated by HDAC8

Abstract After a peripheral nerve injury, Schwann cells (SCs), the myelinating glia of the peripheral nervous system, convert into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1α) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study indicates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery.

The influence of perceived landscape value on tourists’ behavioral intentions in historical and cultural blocks

Historic cultural blocks are areas where a city’s material cultural heritage and humanistic characteristics converge, showcasing the city’s unique features and preserving rich and complete urban memories. Research on historic blocks primarily involves strategies related to protection, renewal, planning, and enhancement. However, there is a paucity of studies that explore the relationship between landscape value perception and tourist behavioral intentions from the perspective of recreation participants during the development and renewal of historic cultural blocks. This study uses the Zhongshan Road and Sifang Road historic cultural blocks in Qingdao as a case example. By collecting multi-source data such as online texts, tourist questionnaires, and interviews, and employing qualitative analysis and structural equation modeling as quantitative analysis methods, the study reveals the structural relationship between landscape value perception, place identity, and tourist behavioral intentions: (1) Landscape value perception has a significant positive effect on tourist behavioral intentions; (2) Landscape value perception has a significant positive effect on place identity; (3) Place identity, as a mediating variable, does not mediate the relationship between ecological landscape value perception and skill education value perception, but partially mediates the relationship between historical cultural value perception and recreational value perception. Based on the research results, feedback on the development effectiveness of historic cultural blocks from the perspective of recreation participants can be visually obtained. This helps identify the pain points in the renewal and development process, pinpoint the perceptual dimensions of landscape value that need improvement, and effectively enhance the multiple dimensions of landscape value perception in the blocks. This, in turn, activates the tourism vitality of historic cultural blocks and forms a virtuous cycle model for their development.

Iron accelerates MDS progression

The master male sex determinant Gdf6Y of the turquoise killifish arose through allelic neofunctionalization

Abstract Although sex determination is a fundamental process in vertebrate development, it is very plastic. Diverse genes became major sex determinants in teleost fishes. Deciphering how individual sex-determining genes orchestrate sex determination can reveal new actors in sexual development. Here, we demonstrate that the Y-chromosomal copy of the TGF-β family member gdf6 ( gdf6Y ) in Nothobranchius furzeri , an emerging model organism in aging research, gained the function of the male sex determinant through allelic diversification while retaining the skeletal developmental function shared with the X-chromosomal gdf6 allele ( gdf6X ). Concerning sex determination, gdf6Y is expressed by somatic supporting cells of the developing testes. There it induces the male sex in a germ cell-independent manner in contrast to sex determination in zebrafish and the medaka. Looking for downstream effectors of Gdf6Y, we identified besides TGF-β signaling modulators, especially the inhibitor of DNA binding genes id1/2/3 , the mRNA decay activator zfp36l2 as a new GDF6 signaling target.

Exploring factors influencing university students’ entrepreneurial intentions: The role of attitudes, beliefs, and environmental support

Entrepreneurship is an increasingly popular career choice among students, driven by the transformative impact of emerging technologies and evolving professional landscapes. This study focuses on how higher education shapes students’ professional identities and entrepreneurial intentions, particularly among business school students. Utilizing the Theory of Planned Behavior (TPB) as the foundational framework, the study examines the factors influencing entrepreneurial intentions, with a specific emphasis on the moderating role of departmental identification. The primary aim of this research is to explore how students’ identification with their academic departments influences the relationship between entrepreneurial attitude, self-efficacy, and environmental support with entrepreneurial intentions. The study hypothesizes that the stronger the departmental identification, the more significant these relationships become. A survey is conducted among students from several public universities in the eastern provinces of Mainland China, yielding 1,632 valid responses. The results confirm a positive correlation between entrepreneurial attitude, self-efficacy, and environmental support with entrepreneurial intentions. Furthermore, departmental identification moderates these relationships, amplifying the effects when students identify strongly with their academic departments. These findings emphasize the critical role of departmental identity in shaping entrepreneurial aspirations. They highlight the need for higher education institutions to leverage departmental identity as a strategic tool to guide students’ career trajectories. By fostering a supportive academic environment that strengthens departmental identity, institutions can better prepare their students for entrepreneurial success in a rapidly evolving professional world.

Long-term follow-up of the STOPAGO study

Abstract In an open prospective, multicenter study enrolling 48 selected patients with chronic immune thrombocytopenia who achieved complete response for 1 year on thrombopoietin receptor agonists, half of the patients maintained a sustained response off treatment 4 years after treatment discontinuation.

Integrated healthy lifestyle even in late-life mitigates cognitive decline risk across varied genetic susceptibility

AbstractIt remains unclear whether the benefits of adhering to a healthy lifestyle outweigh the effects of high genetic risk on cognitive decline. We examined the association of combined lifestyle factors and genetic risk with changes in cognitive function and six specific dimensions of cognition among older adults from the Chinese Longitudinal Healthy Longevity Survey (1998–2018, n = 18,811, a subset of 6301 participants with genetic information). Compared to participants with an unfavorable lifestyle, those with a favorable lifestyle showed a 46.81% slower rate of cognitive decline, with similar results across most cognitive domains. High genetic risk was associated with a 12.5% faster rate of cognitive decline. Individuals with a high genetic risk and a favorable lifestyle have slower cognitive decline than those with a low genetic risk and an unfavorable lifestyle. These data suggest that the benefits of a favorable lifestyle outweigh genetic factors, and therefore that adhering to a favorable lifestyle may offset the genetic risk for accelerated cognitive decline.

Self- versus clinician-collected swabs in anal cancer screening: A clinical trial

Background Risk of anal cancer is high in certain populations and screening involves collection of anal swabs for HPV DNA and/or cytology testing. However, barriers exist, such as the need for an intimate examination, and stigma around HIV status, sexual orientation, and sexual practices. Self-collected anal swabs (SCA) are a proposed alternative to clinician-collected swabs (CCA) to overcome these barriers. Methods Participants were order-randomised to undergo SCA or CCA first, with a second swab taken immediately afterwards. Sample adequacy was assessed for HPV DNA and cytology testing. CCA was used as the gold standard to calculate sensitivity and specificity of SCA for cytology and HPV results. Acceptability of swab collection was assessed following the procedure. Results There was no significant difference in sample validity for HPV DNA testing between SCA and CCA (p = 0.564). Concordance was >90% for detection of any HR-HPV and HPV16. There was no significant difference in cellular adequacy for cytological testing between SCA and CCA, (p = 0.162). Concordance for cytologic prediction was 88.2% for any cytologic abnormality. Almost half (48.5%) of participants expressed no preference for SCA versus CCA; 15.2% preferred SCA and 35.4% CCA. Conclusions SCA may be an acceptable and feasible alternative to CCA for detecting HPV and cytological abnormalities in a clinic population.

Doubling down on GPRC5D in multiple myeloma

Systematically developing a registry of splice-site creating variants utilizing massive publicly available transcriptome sequence data

Abstract Genomic variants causing abnormal splicing play important roles in genetic disorders and cancer development. Among them, variants that cause the formation of novel splice-sites (splice-site creating variants, SSCVs) are particularly difficult to identify and often overlooked in genomic studies. Additionally, these SSCVs are frequently considered promising candidates for treatment with splice-switching antisense oligonucleotides (ASOs). To leverage massive transcriptome sequence data such as those available from the Sequence Read Archive, we develop a novel framework to screen for SSCVs solely using transcriptome data. We apply it to 322,072 publicly available transcriptomes and identify 30,130 SSCVs. Among them, 5121 SSCVs affect disease-causing variants. By utilizing this extensive collection of SSCVs, we reveal the characteristics of Alu exonization via SSCVs, especially the hotspots of SSCVs within Alu sequences and their evolutionary relationships. We discover novel gain-of-function SSCVs in the deep intronic region of the NOTCH1 gene and demonstrate that their activation can be suppressed using splice-switching ASOs. Collectively, we provide a systematic approach for automatically acquiring a registry of SSCVs, which facilitates the elucidation of novel biological mechanisms underlying splicing and serves as a valuable resource for drug discovery. The catalogs of SSCVs identified in this study are accessible on the SSCV DB ( https://sscvdb.io ).

Examining the risk of delirium in patients hospitalized with COVID-19: Insights from the homeless population

For patients hospitalized with COVID-19, delirium is a serious and under-recognized complication, and people experiencing homelessness (PEH) may be at greater risk. This retrospective cohort study compared delirium-associated risk factors and clinical outcomes between PEH and non-PEH. This study used patient records from 154 hospitals discharged from 2020–2021 from the Texas Inpatient Public Use Data file. Study subjects (n = 878) were patients, aged 18–69 years, who were hospitalized with COVID-19 and were identified as homeless. The baseline group included (n = 176,518) patients with COVID-19 aged 18–69 years who were not homeless. Logistic regression models were used to identify risk factors for delirium. Relevant risk factors included chronic comorbidities, substance use disorders, and traumatic brain injury (TBI). Seven of the delirium-associated risk factors were more prevalent among PEH compared to baseline. PEH had higher rates of TBI, alcohol, cannabis, and opioid use disorders. PEH had significantly higher rates of delirium (10.6% vs. 8.1%; P<0.01). However, PEH had fewer respiratory complications, including pneumonia (48.5% vs. 81.9%; P<0.001) and respiratory failure (28.7% vs. 61.9%; P<0.001), and lower in-hospital mortality (3.3% vs. 9.5%; P<0.001). The anti-viral Remdesivir had a protective effect against delirium (AOR = 0.63; CI: 0.60, 0.66). Mean hospital length of stay (LOS) was more than twice as long for delirious patients compared with non-delirious patients (18.4 days vs. 7.7 days; P<0.001). Delirium greatly increased the risk of in-hospital mortality (AOR = 3.8; CI: 3.6, 4.0). For PEH (n = 29) who died from COVID-19, delirium was present in more than half (52%) of cases. Hospitals should screen PEH for delirium and adopt nursing protocols to prevent delirium and reduce its severity.

Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma

Abstract Despite several approved therapies, multiple myeloma (MM) remains an incurable disease with high unmet medical need. “Off-the-shelf” T-cell bispecific antibodies (TCBs) targeting B-cell maturation antigen (BCMA) and G protein–coupled receptor class C group 5 member D (GPRC5D) have demonstrated high objective response rates in heavily pretreated patients with MM; however, primary resistance, short duration of response, and relapse driven by antigen shift frequently occur. Although GPRC5D represents the most selective target in MM, recent findings indicate antigen loss occurs more frequently than with BCMA. Thus, anti-GPRC5D immunotherapies must hit hard during a short period of time. Here, we characterize forimtamig, a novel GPRC5D-targeting TCB with 2+1 format. Bivalent binding of forimtamig to GPRC5D confers higher affinity than classical 1+1 TCB formats correlating with formation of more stable immunological synapses and higher potency in tumor cell killing and T-cell activation. Using an orthotopic mouse model of MM, forimtamig recruited T effector cells to the bone marrow and induced rapid tumor killing even after the introduction of step-up dosing to mitigate cytokine release. Combination of forimtamig with standard-of-care agents including anti-CD38 antibodies, immunomodulatory drugs, and proteasome inhibitors improved depth and duration of response. The combination of forimtamig with novel therapeutic agents including BCMA TCB and cereblon E3 ligase modulatory drugs was potent and prevented occurrence of GPRC5D -negative tumor relapse. Forimtamig is currently being evaluated in phase 1 clinical trials in patients with relapsed and refractory MM for monotherapy and in combination treatments. This trial was registered at www.ClinicalTrials.gov as #NCT04557150.