Enhanced rock weathering increased soil phosphorus availability and altered root phosphorus-acquisition strategies.

Enhanced rock weathering (ERW) has been proposed as a measure to enhance the carbon (C)-sequestration potential and fertility of soils. The effects of this practice on the soil phosphorus (P) pools and the general mechanisms affecting microbial P cycling, as well as plant P uptake are not well understood. Here, the impact of ERW on soil P availability and microbial P cycling functional groups and root P-acquisition traits were explored through a 2-year wollastonite field addition experiment in a tropical rubber plantation. The results show that ERW significantly increased soil microbial carbon-use efficiency and total P concentrations and indirectly increased soil P availability by enhancing organic P mobilization and mineralization of rhizosheath carboxylates and phosphatase, respectively. Also, ERW stimulated the activities of P-solubilizing (gcd, ppa and ppx) and mineralizing enzymes (phoADN and phnAPHLFXIM), thus contributing to the inorganic P solubilization and organic P mineralization. Accompanying the increase in soil P availability, the P-acquisition strategy of the rubber fine roots changed from do-it-yourself acquisition by roots to dependence on mycorrhizal collaboration and the release of root exudates. In addition, the direct effects of ERW on root P-acquisition traits (such as root diameter, specific root length, and mycorrhizal colonization rate) may also be related to changes in the pattern of belowground carbon investments in plants. Our study provides a new insight that ERW increases carbon-sequestration potential and P availability in tropical forests and profoundly affects belowground plant resource-use strategies.

Advancing Neurological Health: Insights into Aging, Immunity, and Vascular Dynamics.

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Popping and Locking: Balanced Rigidity and Porosity of Zeolitic Imidazolate Frameworks for High-Productivity Methane Purification.

Zeolitic imidazolate frameworks (ZIFs) hold great promise in carbon capture, owing to their structural designability and functional porosity. However, intrinsic linker dynamics limit their pressure-swing adsorption application to biogas upgrading and methane purification. Recently, a functionality-locking strategy has shown feasibility in suppressing such dynamics. Still, a trade-off between structural rigidity and uptake capacity remains a key challenge for optimizing their high-pressure CO2/CH4 separation performance. Here, we report a sequential structural locking (SSL) strategy for enhancing the CO2 capture capacity and CH4 purification productivity in dynamic ZIFs (dynaZIFs). Specifically, we isolated multiple functionality-locked phases, ZIF-78-lt, -ht1, and -ht2, by activation at 50, 160, and 210 °C, respectively. We observed multiple-level locking through gas adsorption and powder X-ray diffraction. We uncovered an SSL mechanism dominated by linker-linker π-π interactions that transit to C-H···O hydrogen bonds with binding energies increasing from -0.64 to -2.77 and -5.72 kcal mol-1, respectively, as evidenced by single-crystal X-ray diffraction and density functional theory calculations. Among them, ZIF-78-ht1 exhibits the highest CO2 capture capacity (up to 18.6 mmol g-1) and CH4 purification productivity (up to 7.6 mmol g-1) at 298 K and 30 bar. These findings provide molecular and energetic insights into leveraging framework flexibility through the SSL mechanism to optimize porous materials' separation performance.

Encoding ordered structural complexity to covalent organic frameworks.

Installing different chemical entities onto crystalline frameworks with well-defined spatial distributions represents a viable approach to achieve ordered and complex synthetic materials. Herein, a covalent organic framework (COF-305) is constructed from tetrakis(4-aminophenyl)methane and 2,3-dimethoxyterephthalaldehyde, which has the largest unit cell and asymmetric unit among known COFs. The ordered complexity of COF-305 is embodied by nine different stereoisomers of its constituents showing specific sequences on topologically equivalent sites, which can be attributed to its building blocks deviating from their intrinsically preferred simple packing geometries in their molecular crystals to adapt to the framework formation. The insight provided by COF-305 supplements the principle of covalent reticular design from the perspective of non-covalent interactions and opens opportunities for pursuing complex chemical sequences in molecular frameworks.

Global, regional, and national burden of non-communicable diseases attributable to occupational asbestos exposure 1990-2019 and prediction to 2035: worsening or improving?

Understanding the burden associated with occupational asbestos exposure on a global and regional scale is necessary to implement coordinated prevention and control strategies. By the GBD Study 2019, we conducted a comprehensive assessment of the non-communicable diseases burden attributable to occupational asbestos exposure. In 2019, 239,330 deaths and 4,189,000 disability-adjusted life years (DALYs) worldwide due to occupational asbestos exposure occurred. 1990-2019, deaths and DALYs attributed to occupational asbestos exposure increased by 65.65% and 43.66%, respectively. Age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) decreased, with the most rapid declines in high Socio-Demographic Index (SDI) regions, with average annual percent change (AAPC) of - 1.05(95%CI: -1.2, -0.89) and -1.53(95%CI: -1.71, -1.36), respectively. Lung cancer, mesothelioma and ovarian cancer were the top three contributors to the increase in deaths and DALYs, accounting for more than 96%. AAPCs of ASMR and ASDR were positively associated with SDI. Global deaths from occupational asbestos exposure were predicted to increase and ASMR to decrease by 2035, mostly in males. Due consideration should be given to the susceptibility of the elderly, the lag of asbestos onset, and the regional differences, and constantly improve the prevention and control measures of occupational asbestos exposure and related diseases.

Global burden of maternal disorders attributable to malnutrition from 1990 to 2019 and predictions to 2035: worsening or improving?

Background and aims: Maternal malnutrition is a major global public health problem that can lead to serious maternal diseases. This study aimed to analyze and predict the spatio-temporal trends in the burden of maternal disorders attributable to malnutrition, and to provide a basis for scientific improvement of maternal malnutrition and targeted prevention of maternal disorders. Methods: Data on maternal disorders attributable to malnutrition, including number of deaths, disability-adjusted life years (DALYs), population attributable fractions (PAFs), age-standardized mortality rates (ASMRs), and age-standardized DALY rates (ASDRs) were obtained from the Global Burden of Disease Study 2019 to describe their epidemiological characteristics by age, region, year, and type of disease. A log-linear regression model was used to calculate the annual percentage change (AAPC) of ASMR or ASDR to reflect their temporal trends. Bayesian age-period-cohort model was used to predict the number of deaths and mortality rates to 2035. Results: Global number of deaths and DALYs for maternal disorders attributable to malnutrition declined by 42.35 and 41.61% from 1990 to 2019, with an AAPC of -3.09 (95% CI: -3.31, -2.88) and -2.98 (95% CI: -3.20, -2.77) for ASMR and ASDR, respectively. The burden was higher among younger pregnant women (20-29 years) in low and low-middle socio-demographic index (SDI) regions, whereas it was higher among older pregnant women (30-39 years) in high SDI region. Both ASMR and ASDR showed a significant decreasing trend with increasing SDI. Maternal hemorrhage had the highest burden of all diseases. Global deaths are predicted to decline from 42,350 in 2019 to 38,461 in 2035, with the ASMR declining from 1.08 (95% UI: 0.38, 1.79) to 0.89 (95% UI: 0.47, 1.31). Conclusion: Maternal malnutrition is improving globally, but in the context of the global food crisis, attention needs to be paid to malnutrition in low SDI regions, especially among young pregnant women, and corresponding measures need to be taken to effectively reduce the burden of disease.

MiR-136-5p in cancer: Roles, mechanisms, and chemotherapy resistance.

MicroRNAs (miRNAs) have emerged as important regulators of gene expression, and the deregulation of their activity has been linked to the onset and progression of a variety of human malignancies. Among these miRNAs, miR-136-5p has attracted significant attention due to its diverse roles in cancer biology. Mostly, miR-136-5p is downregulated in malignancies. It could inhibit viability, proliferation, migration, invasion and promote apoptosis of tumor cells. This review article provides a comprehensive overview of the current understanding of miR-136-5p in different sorts of human cancers: genital tumors, head and neck tumors, tumors from the digestive and urinary systems, skin cancers, neurologic tumors, pulmonary neoplasms and other cancers by discussing its molecular mechanisms, functional roles, and impact in chemotherapies. In conclusion, miR-136-5p could be a promising new biomarker and potential clinical therapeutic target.

A personalized biomimetic dual-drug delivery system via controlled release of PTH1-34 and simvastatin for in situ osteoporotic bone regeneration.

Patients with osteoporosis often encounter clinical challenges of poor healing after bone transplantation due to their diminished bone formation capacity. The use of bone substitutes containing bioactive factors that increase the number and differentiation of osteoblasts is a strategy to improve poor bone healing. In this study, we developed an in situ dual-drug delivery system containing the bone growth factors PTH1-34 and simvastatin to increase the number and differentiation of osteoblasts for osteoporotic bone regeneration. Our system exhibited ideal physical properties similar to those of natural bone and allowed for customizations in shape through a 3D-printed scaffold and GelMA. The composite system regulated the sustained release of PTH1-34 and simvastatin, and exhibited good biocompatibility. Cell studies revealed that the composite system reduced osteoblast death, and promoted expression of osteoblast differentiation markers. Additionally, by radiographic analysis and histological observation, the dual-drug composite system demonstrated promising bone regeneration outcomes in an osteoporotic skull defect model. In summary, this composite delivery system, comprising dual-drug administration, holds considerable potential for bone repair and may serve as a safe and efficacious therapeutic approach for addressing bone defects in patients with osteoporosis.

Hemorrhagic stroke-induced subtype of inflammatory reactive astrocytes disrupts blood-brain barrier.

Astrocytes undergo disease-specific transcriptomic changes upon brain injury. However, phenotypic changes of astrocytes and their functions remain unclear after hemorrhagic stroke. Here we reported hemorrhagic stroke induced a group of inflammatory reactive astrocytes with high expression of Gfap and Vimentin, as well as inflammation-related genes lipocalin-2 (Lcn2), Complement component 3 (C3), and Serpina3n. In addition, we demonstrated that depletion of microglia but not macrophages inhibited the expression of inflammation-related genes in inflammatory reactive astrocytes. RNA sequencing showed that blood-brain barrier (BBB) disruption-related gene matrix metalloproteinase-3 (MMP3) was highly upregulated in inflammatory reactive astrocytes. Pharmacological inhibition of MMP3 in astrocytes or specific deletion of astrocytic MMP3 reduced BBB disruption and improved neurological outcomes of hemorrhagic stroke mice. Our study demonstrated that hemorrhagic stroke induced a group of inflammatory reactive astrocytes that were actively involved in disrupting BBB through MMP3, highlighting a specific group of inflammatory reactive astrocytes as a critical driver for BBB disruption in neurological diseases.

CCL5 mediated astrocyte-T cell interaction disrupts blood-brain barrier in mice after hemorrhagic stroke.

The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how astrocytes interact with immune cells and the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing in astrocytes that were activated by interleukin-1α (IL-1α), tumor necrosis factor α (TNFα), and complement component 1q (C1q) treatment, we found CCL5 was among the top upregulated genes. Immunostaining and western blot results demonstrated that CCL5 was increased in mice brain after hemorrhagic stroke. Flow cytometry showed that knockout of astrocytic CCL5 reduced the infiltration of CD8+ but not CD4+ T and myeloid cells into the brain (p < 0.05). In addition, knockout CCL5 in astrocytes increased tight junction-related proteins ZO-1 and Occludin expression; reduced Evans blue leakage, perforin and granzyme B expression; improved neurobehavioral outcomes in hemorrhagic stroke mice (p < 0.05), while transplantation of CD8+ T cells reversed these protective effects. Moreover, co-culture of CD8+ T cells with bEnd.3 cells induced the apoptosis of bEnd.3 cells, which was rescued by inhibiting perforin. In conclusion, our study suggests that CCL5 mediated crosstalk between astrocytes and CD8+ T cells represents an important therapeutic target for protecting BBB in stroke.

Porous carboxymethyl cellulose nanocrystalline imprinted composite aerogels for selective adsorption of gadolinium.

Gadolinium is widely applied in medical and high-tech materials because of special magnetic properties. Recovery of gadolinium from waste rare earth products has both economic and environmental value. In this experiment, honeycomb porous composite aerogels were constructed using sericin and sodium alginate mixed with functionally modified carboxymethylated cellulose nanocrystals for the adsorption and separation of gadolinium ions. There were large numbers of carboxyl groups as well as hydroxyl groups on the surface of sodium alginate and filamentous protein, which provided more sites for the adsorption of gadolinium ions. Besides, a stable honeycomb structure appeared on the surface of composite aerogels when the mixture of filamentous protein and sodium alginate was 1:1, which increased the specific surface area of materials to 140.65 m2 g-1. Additionally, the imprinted composite aerogels Ic-CNC/SSA were prepared by virtue of the imprinting technology, enhancing the adsorption selectivity of composite aerogels for gadolinium. The adsorption experiments revealed that the maximum adsorption capacity of Ic-CNC/SSA reached 93.41 mg g-1 at pH 7.0, indicating good selective adsorption of gadolinium ions. In summary, such composite aerogels provide great potential and reference value for the selective adsorption of gadolinium ions in industry.

Selective Adsorption of Gadolinium by Nitrogen-Doped Carboxymethylated Cellulose Nanocrystalline Carbon Aerogels Functionalized in the Ammonia-Urea System.

In this paper, an ammonia-urea system was developed to induce the shedding of carboxymethylcellulose carbon aerogels to form defects, and the specific surface area of the aerogels was significantly increased after carbonization, and the three-dimensional disordered pore structure of cellulose was preserved. The material showed the selective adsorption of gadolinium ions using the carboxylate active sites provided by carboxymethylation and the microporous or mesoporous structures formed after carbon burning. The successful synthesis of the material was demonstrated by relevant characterization, and the results of static adsorption experiments showed that the material was more consistent with the quasi second-order kinetic model at pH = 5.0. The maximum adsorption capacity was 99.65 mg g-1. The material showed a high adsorption capacity for gadolinium ions in the presence of competing ions and maintained 84.07% of the adsorption performance after five adsorption cycles. The simple use of urea ensured that the cellulose maintained its pore structure, and the specific surface area was greatly increased after carbonization, which provided a feasible direction for the industrial adsorption and recycling of rare-earth elements for reuse.

Corrigendum: Global burden of non-communicable chronic diseases associated with a diet low in fruits from 1990 to 2019.

[This corrects the article DOI: 10.3389/fnut.2023.1202763.].

Photochemical α-selective radical ring-opening reactions of 1,3-disubstituted acyl bicyclobutanes with alkyl halides: modular access to functionalized cyclobutenes.

Although ring-opening reactions of bicyclobutanes bearing electron-withdrawing groups, typically with ß-selectivity, have evolved as a powerful platform for synthesis of cyclobutanes, their application in the synthesis of cyclobutenes remains underdeveloped. Here, a novel visible light induced α-selective radical ring-opening reaction of 1,3-disubstituted acyl bicyclobutanes with alkyl radical precursors for the synthesis of functionalized cyclobutenes is described. In particular, primary, secondary, and tertiary alkyl halides are all suitable substrates for this photocatalytic transformation, providing ready access to cyclobutenes with a single all-carbon quaternary center, or with two contiguous centers under mild reaction conditions.

Preparation of imprinted bacterial cellulose aerogel with intelligent modulation of thermal response stimulation for selective adsorption of Gd(III) from wastewater.

Research on recycling of used rare earth elements has been of great interest. Adsorption is one of the advantageous methods to recover gadolinium with high value. In the process of adsorption and separation of gadolinium from materials, the selectivity of materials for gadolinium can be significantly improved by using ion imprinting technique. However, gadolinium elution process is a traditional pickling process, which may affect the construction of imprinting sites. In this study, bacterial cellulose with three-dimensional spatial structure was used as the base material of aerogel material, and functional materials containing a large number of carboxyl groups were introduced by chemical grafting method. In combination with ion imprinting technology and N-polyacrylamide as intelligent temperature control valve, intelligent imprinting aerogel (PNBC-IIPS) with specific selectivity to gadolinium was prepared. The properties of aerogel materials were analyzed by SEM, FT-IR, and BET characterization. The experimental analysis shows that the desorption of gadolinium can be achieved by controlling the temperature change. The adsorption experiments show that PNBC-IIPS can selectively adsorb gadolinium ions from aqueous solution. The maximum adsorption capacity reached 95.51 mg g-1. Compared with unimprinted aerogel, the maximum adsorption capacity of gadolinium ion is significantly increased, which proves that the introduced ion imprinting technique plays a key role in the adsorption process. Cyclic experiments show that the adsorption capacity of PNBC-IIPS can still maintain 88% of the original adsorption capacity after 5 times of adsorption and desorption. In conclusion, PNBC-IIPS is a green adsorbent for selective recovery of gadolinium ions.

Successful Treatment of Recurrent Adult-Onset Still's Disease with Tocilizumab: A Case Report and Literature Review.

Adult-onset Still's disease (AOSD) is considered a rare autoimmune inflammatory disorder with an unclear etiology and pathogenesis.The main clinical manifestations of this disease are high fever, joint pain, and transient skin lesions. Physical examination may reveal hepatomegaly, splenomegaly, and lymphadenopathy, while laboratory tests show abnormalities such as elevated white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum ferritin (SF). The lack of specific diagnostic markers contributes to a relatively high rate of clinical misdiagnosis and missed diagnoses.In terms of treatment, glucocorticoids have always been the cornerstone medication, but some patients exhibit suboptimal responses to conventional drug therapy, making disease control challenging. However, as our understanding of the pathogenesis continues to grow, novel therapeutic approaches targeting various cytokines have been gradually identified. In this report, we present a case of successful treatment of recurrent AOSD with tocilizumab (TCZ), along with a concise review of innovative treatment strategies for AOSD based on literature retrieval.

Silver-Catalyzed Dearomative [2π+2σ] Cycloadditions of Indoles with Bicyclobutanes: Access to Indoline Fused Bicyclo[2.1.1]hexanes.

Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles and bicyclobutane precursors is described. The strain-release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale-up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.

C(sp2)-H cyclobutylation of hydroxyarenes enabled by silver-π-acid catalysis: diastereocontrolled synthesis of 1,3-difunctionalized cyclobutanes.

Ring-opening of bicyclo[1.1.0]butanes (BCBs) is emerging as a powerful strategy for 1,3-difunctionalized cyclobutane synthesis. However, reported radical strain-release reactions are typically plagued with diastereoselectivity issues. Herein, an atom-economic protocol for the highly chemo- and diastereoselective polar strain-release ring-opening of BCBs with hydroxyarenes catalyzed by a π-acid catalyst AgBF4 has been developed. The use of readily available starting materials, low catalyst loading, high selectivity (up to >98 : 2 d.r.), a broad substrate scope, ease of scale-up, and versatile functionalizations of the cyclobutane products make this approach very attractive for the synthesis of 1,1,3-trisubstituted cyclobutanes. Moreover, control experiments and theoretical calculations were performed to illustrate the reaction mechanism and selectivity.

Efficacy and safety of laser-related therapy for melasma: A systematic review and network meta-analysis.

BACKGROUND: Melasma is a prevalent, persistent hyperpigmentation disorder that negatively affects the psychological health of patients. However, the treatment outcome remains unsatisfactory due to the complexity of pathogenesis, recurrence characteristics, and relatively high morbidity. OBJECTIVES: To compare the performance of laser-related therapies in improving the melasma area severity index (MASI) score of melasma and the occurrence of adverse effects by network meta-analysis (NMA). METHODS: From the inception to November 2022, eligible randomized controlled trials were identified. Two investigators independently searched relevant studies from PUBMED, EMBASE, and the Cochrane Library database. RESULTS: A total of 39 clinical studies with 1394 participants were eligible for enrollment. For efficacy, the NMA demonstrated that Q-switched Nd: YAG laser + topical medications (QSND+TM) was superior to Q-switched Nd:YAG laser (QSND) [MD = -4.21 (-6.80, -1.63)], Er: YAG laser + topical medications (ERYL+TM) [MD = -3.52 (-6.84, -0.19)], and picosecond laser + topical medications (PICO+TM) [MD = -4.80 (-9.33, -0.27)]. The microneedling + topical medications (MN+TM) was superior to picosecond laser (PICO) [MD = -5.26 (-10.44, -0.08)] and topical medications (TM) [MD = -5.22 (-9.20, -1.23)]. The top five of the surface under the cumulative ranking curve value (SUCRA) are Q-switched Nd:YAG laser + topical medications (QSND+TM 85.9%), oral tranexamic acid (oTA 80.1%), microneedling + topical medications (MN+TM 79.7%), Q-switched Nd:YAG laser + intense pulse light (QSND+IPL 78.9%), and fractional carbon dioxide laser + topical medications (FCDL+TM 70.5%). CONCLUSIONS: In conclusion, the Qs-Nd:YAG laser with topical medications is the first choice for treating melasma according to the SUCRA value. Among the three treatment modalities, namely MN + TM, PICO, and TM, our recommendation favors MN+TM as the superior choice for enhancing the curative efficacy in melasma. However, the actual clinical choice should also take into account the adverse effects, the skin type of the patient, the duration of the disease, and other relevant factors.

Global burden of non-communicable chronic diseases associated with a diet low in fruits from 1990 to 2019.

Background: The aim of this study was to assess the global burden of disease from non-communicable chronic diseases (NCD) due to diet low in fruits from 1990 to 2019. Methods: Based on data from the Global Burden of Disease (GBD) 2019, the global burden of disease due to diet low in fruits was analyzed for each country or region, disaggregated by disease type, age, sex, and year. The number of deaths and disability-adjusted life years (DALYs), population attributable fraction (PAF), age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were calculated, and the average annual percentage change (AAPC) was calculated to describe trends in ASMR and ASDR from 1990 to 2019. Results: From 1990 to 2019, the number of deaths and DALYs due to diet low in fruits increased by 31.5 and 27.4%, respectively. Among the tertiary diseases, ischemic heart disease, stroke, and diabetes and kidney disease were the top three contributors to the global increase in deaths and DALYs. However, both ASMR and ASDR showed a decreasing trend. The fastest decline in ASMR and ASDR was in stroke, with AAPC of -2.13 (95% CI: -2.22, -2.05, p < 0.05) and -0.56 (95% CI: -0.62, -0.51, p < 0.05), respectively. For GBD regions, high PAF occurred mainly in South Asia, Oceania, and sub-Saharan Africa. Age-specific PAF for stroke and ischemic heart disease death attributable to diet low in fruits was significantly negatively associated with age. Diet low in fruits related ASMR and ASDR showed an M-shaped relationship with the socio-demographic index (SDI), but with an overall decreasing trend. Conclusion: The number of deaths and DALYs due to diet low in fruits continues to increase. Therefore, early nutritional interventions should be implemented by the relevant authorities to reduce the burden of diseases caused by diet low in fruits.