Deficiency of CAMSAP2 impairs olfaction and the morphogenesis of mitral cells.

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.

The nitrate-inducible NAC transcription factor NAC056 controls nitrate assimilation and promotes lateral root growth in Arabidopsis thaliana.

Nitrate can affect many aspects of plant growth and development, such as promoting root growth and inhibiting the synthesis of secondary metabolites. However, the mechanisms underlying such effects and how plants can integrate nitrate signals and root growth needs further exploration. Here, we identified a nitrate-inducible NAC family transcription factor (TF) NAC056 which promoted both nitrate assimilation and root growth in Arabidopsis. NAC056 is a nuclear-localized transcription activator, which is predominantly expressed in the root system and hypocotyl. Using the yeast one-hybrid assay, we identified the NAC056-specific binding sequence (NAC56BM), T [T/G/A] NCTTG. We further showed that the nac056 mutant compromised root growth. NAC056 overexpression promotes LR Initiation and nitrate deficiency tolerance. Using RNA sequencing analysis and in vitro biochemical experiment, we found NAC056 regulated the expression of genes required for NO3- assimilation, directly targeting the key nitrate assimilation gene NIA1. In addition, mutation of NIA1 suppresses LR development and nitrate deficiency tolerance in the 35S::NAC056 transgenic plants. Therefore, NAC056 mediates the response of plants to environmental nitrate signals to promote root growth in Arabidopsis.

Identification of a novel fusion gene, RARA::ANKRD34C, in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.

Transcriptional silencing of fetal hemoglobin expression by NonO.

Human fetal globin (γ-globin) genes are developmentally silenced after birth, and reactivation of γ-globin expression in adulthood ameliorates symptoms of hemoglobin disorders, such as sickle cell disease (SCD) and ß-thalassemia. However, the mechanisms by which γ-globin expression is precisely regulated are still incompletely understood. Here, we found that NonO (non-POU domain-containing octamer-binding protein) interacted directly with SOX6, and repressed the expression of γ-globin gene in human erythroid cells. We showed that NonO bound to the octamer binding motif, ATGCAAAT, of the γ-globin proximal promoter, resulting in inhibition of γ-globin transcription. Depletion of NonO resulted in significant activation of γ-globin expression in K562, HUDEP-2, and primary human erythroid progenitor cells. To confirm the role of NonO in vivo, we further generated a conditional knockout of NonO by using IFN-inducible Mx1-Cre transgenic mice. We found that induced NonO deletion reactivated murine embryonic globin and human γ-globin gene expression in adult ß-YAC mice, suggesting a conserved role for NonO during mammalian evolution. Thus, our data indicate that NonO acts as a novel transcriptional repressor of γ-globin gene expression through direct promoter binding, and is essential for γ-globin gene silencing.

A novel "on-off" SERS nanoprobe based on sulfonated cellulose nanofiber-Ag composite for selective determination of NADH in human serum.

A novel S-CNF-based nanocomposite was created using sulfonated cellulose nanofiber (S-CNF) to enable the detection of NADH in serum by surface-enhanced Raman spectroscopy (SERS). The numerous hydroxyl and sulfonic acid groups on the S-CNF surface absorbed silver ions and converted them to silver seeds, which formed the load fulcrum. After adding a reducing agent, silver nanoparticles (Ag NPs) were firmly adhered to the S-CNF surface to form stable 1D "hot spots." The S-CNF-Ag NP substrate demonstrated outstanding SERS performance, including good uniformity with an RSD of 6.88% and an enhancement factor (EF) of 1.23 × 107. Owing to the anionic charge repulsion effect, the S-CNF-Ag NP substrate still maintains remarkable dispersion stability after 12 months of preservation. Finally, S-CNF-Ag NPs' surface was modified with 4-mercaptophenol (4-MP), a special redox Raman signal molecule, to detect reduced nicotinamide adenine dinucleotide (NADH). The results showed that the detection limit (LOD) of NADH was 0.75 µM; a good linear relationship (R2 = 0.993) was established in the concentration range 10-6 - 10-2 M. The SERS nanoprobe enabled rapid detection of NADH in human serum without any complicated sample pretreatment and provides a new potential to detect biomarkers.

Overexpression of a small GTP-binding protein Ran1 in Arabidopsis leads to promoted elongation growth and enhanced disease resistance against P. syringae DC3000.

Plants resist infection through an innate immune response, which is usually associated with slowing of growth. The molecular mechanisms underlying the trade-off between plant growth and defense remain unclear. The present study reveals that growth/defense trade-offs mediated by gibberellin (GA) and salicylic acid (SA) signaling pathways are uncoupled during constitutive overexpression of transgenic AtRAN1 and AtRAN1Q72L (active, GTP-locked form) Arabidopsis plants. It is well known that the small GTP-binding protein Ran (a Ras-related nuclear protein) functions in the nucleus-cytoplasmic transport of proteins. Although there is considerable evidence indicating that nuclear-cytoplasmic partitioning of specific proteins can participate in hormone signaling, the role of Ran-dependent nuclear transport in hormone signaling is not yet fully understood. In this report, we used a combination of genetic and molecular methods to reveal whether AtRAN1 is involved in both GA and SA signaling pathways. Constitutively overexpressed AtRAN1 promoted both elongation growth and the disease resistance response, whereas overexpression of AtRAN1Q72L in the atran2atran3 double mutant background clearly inhibited elongation growth and the defense response. Furthermore, we found that AtRAN1 coordinated plant growth and defense by promoting the stability of the DELLA protein RGA in the nucleus and by modulating NPR1 nuclear localization. Interestingly, genetically modified rice (Oryza sativa) overexpressing AtRAN1 exhibited increased plant height and yield per plant. Altogether, the ability to achieve growth/defense trade-offs through AtRAN1 overexpression provides an approach to maximizing crop yield to meet rising global food demands.

PDGFD switches on stem cell endothelial commitment.

The critical factors regulating stem cell endothelial commitment and renewal remain not well understood. Here, using loss- and gain-of-function assays together with bioinformatic analysis and multiple model systems, we show that PDGFD is an essential factor that switches on endothelial commitment of embryonic stem cells (ESCs). PDGFD genetic deletion or knockdown inhibits ESC differentiation into EC lineage and increases ESC self-renewal, and PDGFD overexpression activates ESC differentiation towards ECs. RNA sequencing reveals a critical requirement of PDGFD for the expression of vascular-differentiation related genes in ESCs. Importantly, PDGFD genetic deletion or knockdown increases ESC self-renewal and decreases blood vessel densities in both embryonic and neonatal mice and in teratomas. Mechanistically, we reveal that PDGFD fulfills this function via the MAPK/ERK pathway. Our findings provide new insight of PDGFD as a novel regulator of ESC fate determination, and suggest therapeutic implications of modulating PDGFD activity in stem cell therapy.

Screening T-Cell Activity via a Photodetachable DNA-Copolymer Nanocage and Its Therapeutic Application.

Screening T-cell activity and selecting active ones from large ex vivo-expanded populations before reinfusion is important for the success of T-cell therapy. Cytokine secretion is the evaluation criterion of cell immune activity. Cell membrane-anchored probes and microchamber-based techniques have been used to screen cytokine secretion at the single-cell level. However, they are either easily affected by nearby cells' secretion or lack of single-cell encapsulation efficiency. Here, we design a photodetachable DNA-copolymer nanocage on the cell membrane for screening the activities of ex vivo-expanded T cells by in-situ monitoring cytokine interferon-gamma (IFN-γ) secretion. The ones with good immune activity are selected for therapeutic application. DNA-copolymer nanocage is self-assembled on a cell membrane to encapsulate a single T cell. A self-quenched IFN-γ recognition aptamer is contained in the DNA-copolymer nanocage, which recovers fluorescence in response to IFN-γ secretion to indicate individual T-cell activity. The active T cells are collected after fluorescence-activated cell sorting, irradiated with 5 min UV light to detach nanocage from the cell membrane, and continuously cocultured with downstream cells. The selected Jurkat cells and CD19 CAR-T cells showed improved capabilities for downstream cell activation and cancer cell killing. The cell membrane-detachable DNA-copolymer nanocage-based T-cell activity screening and selection would have promising applications in T-cell therapy.

Karrikin signaling regulates hypocotyl shade avoidance response by modulating auxin homeostasis in Arabidopsis.

Shade affects all aspects of plant growth and development, including seed germination, hypocotyl elongation, petiole growth, leaf hyponasty, and flowering time. Here, we found that mutations in the key Arabidopsis karrikins signal perception-associated KARRIKIN INSENSITIVE 2 (KAI2) gene, encoding an α/ß-fold hydrolase, and the MORE AXILLARY GROWTH 2 (MAX2) gene, encoding an F-box protein, led to greater hypocotyl elongation under shade avoidance conditions. We further verified that these phenotypes were caused by perception of the endogenous KAI2-ligands (KLs), and that this phenotype is independent of strigolactone biosynthetic or signaling pathways. Upon perception of a KL, it is probable that the target protein forms a complex with the KAI2/MAX2 proteins, which are degraded through the action of the 26S proteasome. We demonstrated that SUPPRESSOR OF MAX2-1 (SMAX1) is the degradation target for the KAI2/MAX2 complex in the context of shade avoidance. KAI2 and MAX2 require SMAX1 to limit the hypocotyl growth associated with shade avoidance. Treatment with l-kynurenine, an inhibitor of auxin accumulation, partially restored elongation of kai2 mutant hypocotyls under simulated shade. Furthermore, KAI2 is involved in regulating auxin accumulation and polar auxin transport, which may contribute to the hypocotyl shade response. In addition, SMAX1 gene overexpression promoted the hypocotyl shade response. RNA-sequencing analysis revealed that SMAX1-overexpression affected the expression of many auxin homeostasis genes, especially under simulated shade. Altogether, our data support the conclusion that KL signaling regulates shade avoidance by modulating auxin homeostasis in the hypocotyl.

Transcription factor CDF4 promotes leaf senescence and floral organ abscission by regulating abscisic acid and reactive oxygen species pathways in Arabidopsis.

Leaf senescence is a highly complex developmental process that is tightly controlled by multiple layers of regulation. Abscisic acid (ABA) and reactive oxygen species (ROS) are two well-known factors that promote leaf senescence. We show here that the transcription factor CDF4 positively regulates leaf senescence. Constitutive and inducible overexpression of CDF4 accelerates leaf senescence, while knockdown of CDF4 delays it. CDF4 increases endogenous ABA levels by upregulating the transcription of the ABA biosynthesis genes 9-cis-epoxycarotenoid dioxygenase 2, 3 (NCED2, 3) and suppresses H2 O2 scavenging by repressing expression of the catalase2 (CAT2) gene. NCED2, 3 knockout and CAT2 overexpression partially rescue premature leaf senescence caused by CDF4 overexpression. We also show that CDF4 promotes floral organ abscission by activating the polygalacturonase PGAZAT gene. Based on these results, we propose that the levels of CDF4, ABA, and ROS undergo a gradual increase driven by their interlinking positive feedback loops during the leaf senescence and floral organ abscission processes.

Bortezomib activation of mTORC1 pathway mediated by NOX2-drived reactive oxygen species results in apoptosis in primary dorsal root ganglion neurons.

Bortezomib (Bort), a chemotherapeutic agent, is widely used for the clinical treatment of cancers. However, Bort-induced peripheral neurotoxicity (BIPN) significantly restricts its clinical application, which is difficult to deal with since the underlying mechanisms of BIPN are unclear. Here, we showed that Bort activates mTORC1 pathway leading to dorsal root ganglion (DRG) neuronal apoptosis. Inhibition of mTORC1 with rapamycin or knockdown of raptor, regulatory-associated protein of mTORC1, with shRNA dramatically rescued the cells from Bort-caused apoptosis. In addition, we found that Bort-activated mTORC1 pathway was attributed to Bort elevation of reactive oxygen species (ROS). This is supported by the evidence that using ROS scavenger N-acetyl cysteine (NAC) significantly alleviated Bort-activated mTORC1 pathway. Furthermore, we revealed that upregulation of NOX2 contributed to Bort-elicited ROS overproduction, leading to mTORC1 pathway-dependent apoptosis in DRG neurons. Inhibition of NOX2 with apocynin remarkably diminished Bort-induced overgeneration of ROS, activation of mTORC1 pathway and apoptosis in the cells. Taken together, these results indicate that Bort activation of mTORC1 pathway mediated by NOX2-drived ROS leads to apoptotic death in DRG neurons. Our findings highlight that manipulation of intracellular ROS level or NOX2 or mTORC1 activity may be exploited for prevention of BIPN.

Platinum prodrug nanoparticles inhibiting tumor recurrence and metastasis by concurrent chemoradiotherapy.

BACKGROUND: Although concurrent chemoradiotherapy (CRT), as one of the most effective antineoplastic therapies in clinic, can successfully inhibit the growth of tumor cells, a risk of developing secondary tumor is still an insurmountable barrier in clinical practice. RESULTS: Herein, a new platinum prodrug composed of tannic acid (TA) and Pt2+ (TA-Pt) complex film was synthesized on the surface of Fe2O3 nanoparticles (NPs) with excellent stability and biocompatibility for enhanced CRT. In this system, TA-Pt complex could respond to the tumor acidic microenvironment and damage the DNA of tumor cells. Moreover, the internal iron core not only improved the effect of subsequent radiotherapy (RT), but also disrupted the iron balance in cells, inducing intracellular ferroptosis and eliminating apoptosis-resistant cells. In vitro and vivo experimental results indicated that more than 90% of tumor cells were depleted and more than 75% of the cured tumor-bearing mice evinced no recurrence or metastasis. CONCLUSIONS: This work offered a new idea for combining the effective chemotherapy, RT and ferroptosis therapy to enhance the curative effect of CRT and inhibit tumor recurrence and metastasis.

Overcoming the blood-brain barrier by using a multistage exosome delivery system to inhibit central nervous system lymphoma.

Due to the presence of blood-brain barrier (BBB), various chemotherapy drugs against B-cell lymphoma cannot be effectively transmitted into the brain, leading to poor prognosis of primary central nervous system lymphoma (PCNSL). Exosomes can cross the BBB as a bio- and immune-compatible drug carrier. In this study, we developed a novel drug delivery system, in which the exosomes (Exo) are conjugated with anti-CD22 monoclonal antibody fragments (CD22-F(ab')2) and encapsulate doxorubicin (DOX) to form CD22-F(ab')2-Exo-DOX. We showed that CD22-F(ab')2-Exo-DOX can cross BBB and deliver DOX precisely to tumor cells. The average apoptosis rate of lymphoma cells was 84.60% ±â€¯10.69%. The tumor-bearing mice treated with CD22-F(ab')2-Exo-DOX have significantly prolonged life expectancy and the enhanced anti-tumor activity. CD22-F(ab')2-Exo-DOX might be ingested by brain microvascular endothelial cells through endocytosis to cross the BBB. Therefore, targeted chemotherapy mediated by CD22-F(ab')2-Exo-DOX is a promising option for the treatment of PCNSL.

Nitrate-responsive OBP4-XTH9 regulatory module controls lateral root development in Arabidopsis thaliana.

Plant root system architecture in response to nitrate availability represents a notable example to study developmental plasticity, but the underlying mechanism remains largely unknown. Xyloglucan endotransglucosylases (XTHs) play a critical role in cell wall biosynthesis. Here we assessed the gene expression of XTH1-11 belonging to group I of XTHs in lateral root (LR) primordia and found that XTH9 was highly expressed. Correspondingly, an xth9 mutant displayed less LR, while overexpressing XTH9 presented more LR, suggesting the potential function of XTH9 in controlling LR development. XTH9 gene mutation obviously alters the properties of the cell wall. Furthermore, nitrogen signals stimulated the expression of XTH9 to promote LRs. Genetic analysis revealed that the function of XTH9 was dependent on auxin-mediated ARF7/19 and downstream AFB3 in response to nitrogen signals. In addition, we identified another transcription factor, OBP4, that was also induced by nitrogen treatment, but the induction was much slower than that of XTH9. In contrast to XTH9, overexpressing OBP4 caused fewer LRs while OBP4 knockdown with OBP4-RNAi or an artificial miRNA silenced amiOBP4 line produced more LR. We further found OBP4 bound to the promoter of XTH9 to suppress XTH9 expression. In agreement with this, both OBP4-RNAi and crossed OBP4-RNAi & 35S::XTH9 lines led to more LR, but OBP4-RNAi & xth9 produced less LR, similar to xth9. Based on these findings we propose a novel mechanism by which OBP4 antagonistically controls XTH9 expression and the OBP4-XTH9 module elaborately sustains LR development in response to nitrate treatment.

[Two cases of coagulation factor â ª deficiency caused by compound heterozygous mutations].

OBJECTIVE: To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients. METHODS: Coagulant assays: activated partial thromboplastin time (APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients' DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. After purified, the products of PCR were sequenced directly, the mutations were detected by comparing with wild sequences and analyzed using some bio-informatics softwares. RESULTS: The two patients were diagnosed with coagulation factor Ⅺ deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FⅪ. The results of APTT, FⅪ: C were 88.1s, 1.1% and 107.1s, 3.8%, and the prolonged APTT could be corrected to normal range 32.9 s and 31.5 s, respectively. Through genetic analysis, we discovered compound heterozygous mutations g.1305-1G>A and g.1325delT in patient 1 and the sequencing results of TA plasmid clones showed that the two mutations were located on different strands of chromosomes. Compound heterozygous mutations g.1124A>G and g.1550C>G were detected in patient 2 resulting in Lys357Arg and Cys482Trp. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed. CONCLUSION: Compound heterozygous mutations g.1305-1G>A, g.1325delT and g.1124A>G, g.1550C>G had been identified in two coagulation factor Ⅺ deficiency patients which might be responsible for their prolonged APTT and low FⅪ: C. To the best of our knowledge, g.1325delT and g.1550C>G have been reported, while g.1124A>G and g.1305-1G>A are reported for the first time in the literature.

[Relationship between sugary food intake and myopia in 11-14 years old Chinese children in 2019-2021].

OBJECTIVE: To investigate the relationship between the intake of sugary foods and the occurrence and development of myopia in children aged 11-14 in China. METHODS: In the 28 urban and rural survey sites in 14 provinces that implemented the "China Children's Nutrition and Health System Survey and Application for 0-18 Years Old" project, a multi-stage stratified random cluster sampling method was adopted, and finally 12 397 adolescent children aged 11 to 14 were selected in the analysis. Demographic characteristics, myopia information and the intake of sugary food(cakes, preserved fruits, candies, chocolates and ice cream) were collected through questionnaires. Multifactor Logistic regression was used to analyze the relationship between sugary food intake and myopia in children. RESULTS: The median daily intake of sugary foods(cakes, preserved fruits, candies, chocolates and ice cream)of 11-14 year old boys and girls in China was 11.4 g and 11.2 g respectively, 33.9% of boys and 34.2% of girls consumed ≥22 g of sugary food every day. The myopia rates of boys with intakes of <2 g, 2-21 g and ≥22 g were 36.0%, 39.2% and 41.6%, and girls' myopia rates were 45.9%, 51.8% and 55.1%. The result of Logistic regression analysis showed that after controlling for confounding factors such as age, gender, region, weekly high-intensity physical activity time, daily screen time, daily sleep time and daily intake of sugary beverages, compared with boys whose daily intake of sugary food was less than 2 g, the risk of myopia for boys whose daily intake of sugary food reached 2-21 g and ≥22 g was 1.18 and 1.23 times, for girls whose daily intake was less than 2 g, the risk of myopia was 1.27 times and 1.38 times for girls whose intake reached 2-21 g and ≥22 g(P<0.05). No matter whether confounding factors were controlled or not, there was no correlation between the intake of sugary foods and the degree of myopia(P>0.05). CONCLUSION: The consumption of sugary food such as cakes, preserved fruits, candies, chocolates and ice cream among children aged 11 to 14 in China is common, and there is a certain degree of positive correlation with the prevalence of myopia, but no correlation is observed with the degree of myopia.

Annexin A5 is essential for PKCθ translocation during T-cell activation.

T-cell activation is a critical part of the adaptive immune system, enabling responses to foreign cells and external stimulus. In this process, T-cell antigen receptor (TCR) activation stimulates translocation of the downstream kinase PKCθ to the membrane, leading to NF-κB activation and thus transcription of relevant genes. However, the details of how PKCθ is recruited to the membrane remain enigmatic. It is known that annexin A5 (ANXA5), a calcium-dependent membrane-binding protein, has been reported to mediate PKCδ activation by interaction with PKCδ, a homologue of PKCθ, which implicates a potential role of ANXA5 involved in PKCθ signaling. Here we demonstrate that ANXA5 does play a critical role in the recruitment of PKCθ to the membrane during T-cell activation. ANXA5 knockout in Jurkat T cells substantially inhibited the membrane translocation of PKCθ upon TCR engagement and blocked the recruitment of CARMA1-BCL10-MALT1 signalosome, which provides a platform for the catalytic activation of IKKs and subsequent activation of canonical NF-κB signaling in activated T cells. As a result, NF-κB activation was impaired in ANXA5-KO T cells. T-cell activation was also suppressed by ANAX5 knockdown in primary T cells. These results demonstrated a novel role of ANXA5 in PKC translocation and PKC signaling during T-cell activation.

The brassinosteroid-responsive xyloglucan endotransglucosylase/hydrolase 19 (XTH19) and XTH23 genes are involved in lateral root development under salt stress in Arabidopsis.

Lateral roots (LRs) are the main component of the root system architecture in Arabidopsis. The plasticity of LR development has an important role in improving plant survival in response to the external environment. Previous studies have revealed a number of genetic pathways that control plant growth in response to environmental stimuli. Here, we find that the xyloglucan endotransglucosylase 19 (XTH19) and XTH23 genes are involved in LR development under salt stress. The density of LRs was decreased in the xth23 single mutant, which was also more sensitive to salt than the wild type, and the xth19xth23 double mutant exhibited additive downregulated LR initiation and salt sensitivity compared with the single mutant. On the contrary, constitutive overexpression of XTH19 or XTH23 caused increased LR densities. Furthermore, XTH19 and XTH23 were induced by salt via the key brassinosteroid signaling pathway transcription factor BES1. In addition, we found that 35S::BES1 increased salt tolerance and the phenotype of xth19xth23 & 35S::BES1 was partially complementary to the wild-type level. In vivo and in vitro assays demonstrated that BES1 acts directly upstream of XTH19 and XTH23 to control their expression. Overall, our results revealed that XTH19 and XTH23 are involved in LR development via the BES1-dependent pathway, and contribute to LR adaptation to salt.

Hotter and drier climate made the Mediterranean Europe and Northern Africa region a shrubbier landscape.

A shift to higher temperatures has left the Mediterranean Europe and Northern Africa (MENA) region more vulnerable to drought and land degradation. We used MODIS LAI (leaf area index) and GPP (gross primary production) deficits, the differences between actual and historical-maximum values, to describe vegetation structural and functional changes and consequential landcover change in response to changing climate conditions during 2001-2019 in the area (20° W-45° E, 20° N-45° N). We found that 1) the vegetation responses varied significantly among eight landcover types with the decreasing importance: forests, savannas, a mosaic of cropland and natural vegetation (CNV), croplands, permanent wetlands, urban land, grasslands, and shrublands, each with distinctive yet overlapping signatures over the ranges of the climate conditions considered. 2) Forests, occupying the coolest and wettest niche, showed the strongest response to severe drought with a lag of 1-3 years and a legacy effect for 10 years. Shrubs, occupying the hottest and driest niche, were the most resilient under a hotter and drier climate. 3) The total areas of savannas and CNV increased by 394,994 and 404,592 km2, respectively, while that of forests decreased by 33,091 km2. Shrublands extended by 287,134 km2 while grasslands and croplands retreated by 490,644 and 225,263 km2. The area of wetlands increased by 49,192 km2, and that of urban land increased by 39,570 km2. A total of 57,649 km2 of barren land became vegetated over the years. Along with higher temperature and more extended period of drought, MENA has evolved towards a shrubbier landscape.

[Association between timing for introducing complementary foods and body composition of children aged 3-5 years in five provinces of China].

OBJECTIVE: To explore the association between different timing of introducing complementary foods during infancy and the body composition of children aged 3-5 years. METHODS: The data was from National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China. A face-to-face interview to caregivers of children was conducted to retrospectively collect timing of introducing complementary foods of children aged 3-5 years. The bioelectrical impedance analysis was used to measure the body composition of children by professionally trained investigators. The exposure variable of the study was the timing of introducing complementary foods(≤5 months old, 6 months old and ≥7 months old). The outcome variables were the fat-free mass, fat-free mass index, body fat mass, body fat mass index, and percentage of body fat. According to age stratification, a multivariate linear regression model was used to calculate the mean, mean difference and 95% CI after adjusting for potential confounders. RESULTS: After adjusting for potential confounders, there were no statistically significant difference in body fat mass, body fat mass index, percentage of body fat and fat-free mass index among different groups of timing for introducing complementary foods for children aged 3-5 years old. For children aged 3-5 years, after adjusting for potential confounders, the difference of fat free mass was statistically significant among children with different timing for introducing of complementary foods(3 years old: 12.89 kg vs. 12.66 kg vs. 12.94 kg, F=4.42, P=0.013; 5 years old: 16.27 kg vs. 16.23 kg vs. 16.66 kg, F=5.40, P=0.005). The fat free mass of children aged 3 years was lower when introducing complementary foods during 6 months of age than at ≤5 months of age(mean difference=-0.23 kg(95% CI-0.45--0.02 kg)). The fat free mass of children aged 5 years was higher when introducing complementary foods at ≥7 months of age than at≤5 months of age(mean difference=0.39 kg(95% CI 0.08-0.70 kg)). CONCLUSION: It is found that the association between timing for introducing complementary foods during infancy and the fat mass indicators of children aged 3 to 5 years was not statistically significant, and the association between timing for introducing complementary foods and fat-free mass may be inconsistent for different fat-free mass indicators.