PagJAZ5 regulates cambium activity through coordinately modulating cytokinin concentration and signaling in poplar.

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.

PagKNAT2/6b promotes shoot branching by attenuating auxin-strigolactone signalling in poplar.

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.

A Multifunctional CaII-EuIII Heterometallic Organic Framework with Sensing and Selective Adsorption in Water.

With increasing global industrialization, it is urgent and challenging to develop multifunctional species for detection and adsorption in the environment. For this purpose, a novel anionic heterometallic organic framework, [(CH3)2NH2][CaEu(CAM)2(H2O)2]·4H2O·4DMF (CaEuCAM), is hydrothermally synthesized based on chelidamic acid (H3CAM). Single crystal analysis shows that CaEuCAM features two different oxygen-rich channels along the c-axis in which one CAM3- bridges two sextuple-coordinated Ca2+ and two octuple-coordinated Eu3+ with a µ4-η1: η1: η1: η1: η1: η1 new chelating and bridging mode. The characteristic bright red emission and superior hydrostability of CaEuCAM under harsh acidic and basic conditions benefit it by acting as a highly sensitive sensor for Fe3+ and 3-nitrophenol (3-NP) with extremely low LODs through remarkable quenching. The combination of experiments and theoretical calculations for sensing mechanisms shows that the competitive absorption and interaction are responsible for Fe3+-induced selective emission quenching, while that for 3-NP is the result of the synergism of host-guest chemistry and the inner filter effect. Meanwhile, the assimilation of negative charge plus channels renders CaEuCAM a highly selective adsorbent for methylene blue (MB) due to a synergy of electrostatic affinity, ion-dipole interaction, and size matching. Of note is the reusability of CaEuCAM toward Fe3+/3-NP sensing and MB adsorption besides its fast response. These findings could be very useful in guiding the development of multifunctional Ln-MOFs for sensing and adsorption applications in water media.

Engrailed 2 serves as a master regulator of the super-enhancer in the TNC gene locus in non-small cell lung cancer.

Engrailed 2 (EN2) is a homeodomain-containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non-small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well-studied oncogenic Tenascin-C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super-enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT-Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC-AKT axis in NSCLC.

Engrailed 2 triggers the activation of multiple phosphorylation-induced signaling pathways in both transcription-dependent and -independent manners.

Homeodomain (HD)-containing proteins are typically recognized as transcription factors. Engrailed 2 (EN2) is an HD-containing protein that is highly expressed in various types of cancers, however, the mechanism underlying the biological function of EN2 is not fully understood. Here, we report a transcription-independent function of EN2 in addition to its role as a transcription factor. EN2 expression leads to the activation of multiple signaling pathways mediated by phosphorylation cascades. A phosphoproteomic analysis revealed that the phosphorylation status of numerous protein sites was altered after EN2 is expressed. Notably, EN2 was shown to interact with a myriad of proteins implicated in phosphorylation signaling cascades, as determined by immunoprecipitation-mass spectrometry (IP-MS). We validated the interaction between EN2 and B55α, the regulatory subunit of the PP2A-B55α complex, and confirmed that the phosphatase activity of the complex was suppressed by EN2 binding. To target EN2-induced malignancy, two kinds of small molecules were utilized to inhibit the EN2-activated NF-κB and AKT signaling pathways. A clear synergistic effect was observed when the activation of the two pathways was simultaneously blocked. Collectively, the data show that EN2 functions in a transcription-independent manner in addition to its role as a transcription factor. This finding may have therapeutic implications in treating esophageal squamous cell carcinoma (ESCC).

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial.

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).

Comprehensive analysis of m6A regulators characterized by the immune microenvironment in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, incurable, degenerative neuromuscular disease that is exacerbated by secondary inflammation. N6-methyladenosine (m6A), the most common base modification of RNA, has pleiotropic immunomodulatory effects in many diseases. However, the role of m6A modification in the immune microenvironment of DMD remains elusive. METHODS: Our study retrospectively analyzed the expression data of 56 muscle tissues from DMD patients and 26 from non-muscular dystrophy individuals. Based on single sample gene set enrichment analysis, immune cells infiltration was identified and the result was validated by flow cytometry analysis and immunohistochemical staining. Then, we described the features of genetic variation in 26 m6A regulators and explored their relationship with the immune mircoenvironment of DMD patients through a series of bioinformatical analysis. At last, we determined subtypes of DMD patients by unsupervised clustering analysis and characterized the molecular and immune characteristics in different subgroups. RESULTS: DMD patients have a sophisticated immune microenvironment that is significantly different from non-DMD controls. Numerous m6A regulators were aberrantly expressed in the muscle tissues of DMD and inversely related to most muscle-infiltrating immune cell types and immune response-related signaling pathways. A diagnostic model involving seven m6A regulators was established using LASSO. Furthermore, we determined three m6A modification patterns (cluster A/B/C) with distinct immune microenvironmental characteristics. CONCLUSION: In summary, our study demonstrated that m6A regulators are intimately linked to the immune microenvironment of muscle tissues in DMD. These findings may facilitate a better understanding of the immunomodulatory mechanisms in DMD and provide novel strategies for the treatment.

Identification of shared and distinct patterns of brain network abnormality across mental disorders through individualized structural covariance network analysis.

BACKGROUND: Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders. METHODS: Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed. RESULTS: Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network. CONCLUSIONS: These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.

Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression.

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Abnormal interhemispheric and intrahemispheric functional connectivity dynamics in drug-naïve first-episode schizophrenia patients with auditory verbal hallucinations.

Numerous studies indicate altered static local and long-range functional connectivity of multiple brain regions in schizophrenia patients with auditory verbal hallucinations (AVHs). However, the temporal dynamics of interhemispheric and intrahemispheric functional connectivity patterns remain unknown in schizophrenia patients with AVHs. We analyzed resting-state functional magnetic resonance imaging data for drug-naïve first-episode schizophrenia patients, 50 with AVHs and 50 without AVH (NAVH), and 50 age- and sex-matched healthy controls. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral parts, and sliding-window analysis was used to calculate voxel-wise interhemispheric and intrahemispheric dynamic functional connectivity density (dFCD). Finally, the correlation analysis was performed between abnormal dFCD variance and clinical measures in the AVH and NAVH groups. Compared with the NAVH group and healthy controls, the AVH group showed weaker interhemispheric dFCD variability in the left middle temporal gyrus (p < .01; p < .001), as well as stronger interhemispheric dFCD variability in the right thalamus (p < .001; p < .001) and right inferior temporal gyrus (p < .01; p < .001) and stronger intrahemispheric dFCD variability in the left inferior frontal gyrus (p < .001; p < .01). Moreover, abnormal contralateral dFCD variability of the left middle temporal gyrus correlated with the severity of AVHs in the AVH group (r = -.319, p = .024). The findings demonstrate that abnormal temporal variability of interhemispheric and intrahemispheric dFCD in schizophrenia patients with AVHs mainly focus on the temporal and frontal cortices and thalamus that are pivotal components of auditory and language pathways.

A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports.

BACKGROUND: Hereditary spastic paraplegia 7 (SPG7) is one of the subtypes of autosomal-recessive hereditary spastic paraplegia, which is a clinically heterogeneous neurodegenerative disorder. SPG7 often displays a complicated phenotype, including optic atrophy, ophthalmoparesis, and impaired emotional communication. In the Chinese population, sporadic cases of SPG7 variant-associated spastic ataxia are rarely reported. CASE PRESENTATION: We carefully analysed the clinical features, imaging and genetic tests of two sporadic patients with SPG7, both from the Hebei region of China. One patient presented with progressive bilateral lower limb weakness, spastic-ataxia and no cognitive impairment. Brain MRI revealed mild cerebellar atrophy. Genetic analysis revealed c.1150_1151insCTAC (p.G384Afs*13) frameshift variant and exon1-3 heterozygous deletion. The other patient presented with progressive bilateral lower limb weakness, ataxia, dysarthria and a mild psychosis associated with persecutory delusions, which drew almost no attention, in addition to mild cognitive impairments characterized by a decrease in verbal memory and executive function. Genetic analysis identified two heterozygous variants in the SPG7 gene: c.1150_1151insCTAC (p.G384Afs*13) and c.1496delC (p.Q500Sfs*13). CONCLUSIONS: The c.1496delC (p.Q500Sfs*13) variant in exon 11 has not been reported before. The c.1150_1151insCTAC variant is speculated to be a hotspot variant in the Chinese population. Patients with SPG7 may have cognitive impairments and psychosis, displaying specific characteristics, which should be of concern.

NOTCH2NLC-related oculopharyngodistal myopathy type 3 complicated with focal segmental glomerular sclerosis: a case report.

BACKGROUND: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal, and distal limb muscle involvement. Recent research showed that GGC repeat expansions in the NOTCH2NLC gene were observed in a proportion of OPDM patients, and these patients were designated as having OPDM type 3 (OPDM3). Heterogeneous neuromuscular manifestations have been described previously in studies of OPDM3; however, kidney involvement in this disease has rarely been reported. CASE PRESENTATION: Here, we report the case of a 22-year-old Chinese patient with typical manifestations of OPDM complicated with focal segmental glomerular sclerosis (FSGS). This patient with sporadic FSGS exhibited distal motor neuropathy and rimmed vacuolar myopathy in clinical and pathological examinations. An expansion of 122 CGG repeats located in the 5' untranslated region (UTR) of the NOTCH2NLC gene was identified as the causative mutation in this patient. The clinical and histopathological findings fully met the criteria for the diagnosis of OPDM3. In addition, intranuclear inclusions were detected in the renal tubule epithelial cells of this patient, indicating that the kidney may also be impaired in NOTCH2NLC-related GGC repeat expansion disorders (NREDs). CONCLUSIONS: Our case report demonstrated the clinicopathological cooccurrence of sporadic FSGS and OPDM3 in a patient, which highlighted that the kidney may show inclusion depositions in OPDM3, thus expanding the clinical spectrum of NREDs.

Kennedy's disease presented with mastication fatigue combined with positive titin antibody: a case report.

BACKGROUND: Spinal and bulbar muscular atrophy (SBMA) is an X-linked recessive hereditary neuromuscular disorder caused by the expanded trinucleotide repeat in the androgen receptors gene. The major clinical manifestations of SBMA consist of weakness in the bulbar and limb muscles, fasciculations, tremors, cramps, sensory impairment, and gynecomastia. However, atypical SBMA cases may lead to misdiagnosis. Muscular fatigue and decremental responses to repetitive nerve stimulation (RNS), despite being observed in some SBMA patients, are usually occurred in MG patients, and patient with the symptom of mastication fatigue was rarely reported. In addition, cardiological investigations have been performed in SBMA patients and several ECG alterations were identified. Here we report an SBMA patient presenting with a rare onset symptom of mastication fatigue, who has been detected with a positive titin antibody in the serum and showed a WPW pattern electrocardiogram. CASE PRESENTATION: The patient showed mildly progressive fatigue in the muscles of mastication over 3 years. Neurological examination showed facial muscle weakness and a wasting tongue with fasciculations, but the weakness, wasting, or fasciculations were not obvious in the limbs. 3-Hz RNS showed a decremental response in bilateral orbicularis oculi. The test of titin antibody was positive in the serum, and the electrocardiogram showed a WPW pattern ECG. Genetic analysis revealed an increased number (39 repeats) of tandem CAG repeats in the AR gene, which confirmed the diagnosis of SBMA. The fatigue symptom was significantly improved after oral pyridostigmine bromide treatment. CONCLUSION: This case calls for more attention to muscular fatigue as the onset symptoms of Kennedy's disease. ECG screening is of importance in SBMA patients and further studies are needed to investigate the titin antibody in SBMA patients as well as other neurogenic disorders.

The clinical, myopathological, and molecular characteristics of 26 Chinese patients with dysferlinopathy: a high proportion of misdiagnosis and novel variants.

BACKGROUND: Dysferlinopathy is an autosomal recessive muscular dystrophy caused by pathogenic variants in the dysferlin (DYSF) gene. This disease shows heterogeneous clinical phenotypes and genetic characteristics. METHODS: We reviewed the clinical and pathological data as well as the molecular characteristics of 26 Chinese patients with dysferlinopathy screened by immunohistochemistry staining and pathogenic variants in DYSF genes. RESULTS: Among 26 patients with dysferlinopathy, 18 patients (69.2%) presented as Limb-girdle Muscular Dystrophy Type R2 (LGMD R2), 4 (15.4%) had a phenotype of Miyoshi myopathy (MM), and 4 (15.4%) presented as asymptomatic hyperCKemia. Fifteen patients (57.7%) were originally misdiagnosed as inflammatory myopathy or other diseases. Fifteen novel variants were identified among the 40 variant sites identified in this cohort. CONCLUSION: Dysferlinopathy is a clinically and genetically heterogeneous group of disorders with various phenotypes, a high proportion of novel variants, and a high rate of misdiagnosis before immunohistochemistry staining and genetic analysis.

The PagKNAT2/6b-PagBOP1/2a Regulatory Module Controls Leaf Morphogenesis in Populus.

Leaf morphogenesis requires precise regulation of gene expression to achieve organ separation and flat-leaf form. The poplar KNOTTED-like homeobox gene PagKNAT2/6b could change plant architecture, especially leaf shape, in response to drought stress. However, its regulatory mechanism in leaf development remains unclear. In this work, gene expression analyses of PagKNAT2/6b suggested that PagKNAT2/6b was highly expressed during leaf development. Moreover, the leaf shape changes along the adaxial-abaxial, medial-lateral, and proximal-distal axes caused by the mis-expression of PagKNAT2/6b demonstrated that its overexpression (PagKNAT2/6b OE) and SRDX dominant repression (PagKNAT2/6b SRDX) poplars had an impact on the leaf axial development. The crinkle leaf of PagKNAT2/6b OE was consistent with the differential expression gene PagBOP1/2a (BLADE-ON-PETIOLE), which was the critical gene for regulating leaf development. Further study showed that PagBOP1/2a was directly activated by PagKNAT2/6b through a novel cis-acting element "CTCTT". Together, the PagKNAT2/6b-PagBOP1/2a module regulates poplar leaf morphology by affecting axial development, which provides insights aimed at leaf shape modification for further improving the drought tolerance of woody plants.

The role of senescence-associated gene101 (PagSAG101a) in the regulation of secondary xylem formation in poplar.

Wood is produced by the accumulation of secondary xylem via proliferation and differentiation of the cambium cells in woody plants. Identifying the regulators involved in this process remains a challenging task. In this study, we isolated PagSAG101a, the homolog of Arabidopsis thaliana SAG101, from a hybrid poplar (Populus alba × Populus glandulosa) clone 84K and investigated its role in secondary xylem development. PagSAG101a was expressed predominantly in lignified stems and localized in the nucleus. Compared with non-transgenic 84K plants, transgenic plants overexpressing PagSAG101a displayed increased plant height, internode number, stem diameter, xylem width, and secondary cell wall thickness, while opposite phenotypes were observed for PagSAG101a knock-out plants. Transcriptome analyses revealed that differentially expressed genes were enriched for those controlling cambium cell division activity and subsequent secondary cell wall deposition during xylem formation. In addition, the tandem CCCH zinc finger protein PagC3H17, which positively regulates secondary xylem width and secondary wall thickening in poplar, could bind to the promoter of PagSAG101a and mediate the regulation of xylem differentiation. Our results support that PagSAG101a, downstream of PagC3H17, functions in wood development.

The clinical, pathological, and genetic characteristics of lipid storage myopathy in northern China.

BACKGROUND: The lipid storage myopathy (LSM) diagnosis is based on the patient's clinical manifestations and muscle pathology. However, when genetic testing is lacking, there is a high rate of misdiagnosis of the disease. This study aimed to investigate the clinical and pathological features of genetically diagnosed LSM in northern China, analyze genetic mutations' characteristics, and improve the LSM diagnostic rate. METHODS: Twenty patients with LSM diagnosed were collected; meanwhile, the clinical data, muscle samples, and routine pathological staining of muscle specimens were collected. The morphological changes of muscle fibers were observed under an optical microscope. RESULTS: Among the included patients, 18 cases had ETFDH (HGNC ID: 3483) mutations, and two had PNPLA2 mutations. Family pedigree verification was performed on three patients with heterozygous mutations in the ETFDH gene complex. Histopathological staining showed that all patients had fine vacuoles in the muscle fibers, and some of them merged to form fissures, and the lipid droplets increased in cells. After therapy, 18 patients were associated with a favorable prognosis, and two patients were ineffective with the treatment of neutral lipid storage myopathy (NLSDM) caused by PNPLA2 mutation. DISCUSSION: The clinical manifestations of LSM are complex and diverse, mainly manifested by proximal muscle weakness and exercise intolerance in the extremities. The pathological images of LSM muscles are abnormal storage of lipid droplets in muscle fibers, primarily involving type I fibers. The LSM patients were mainly multiple acyl-CoA dehydrogenase deficiency (MADD) caused by the ETFDH gene mutation. It is necessary to perform an accurate typing diagnosis of LSM.

Poplar aquaporin PIP1;1 promotes Arabidopsis growth and development.

BACKGROUND: Root hydraulic conductance is primarily determined by the conductance of living tissues to radial water flow. Plasma membrane intrinsic proteins (PIPs) in root cortical cells are important for plants to take up water and are believed to be directly involved in cell growth. RESULTS: In this study, we found that constitutive overexpression of the poplar root-specific gene PtoPIP1;1 in Arabidopsis accelerated bolting and flowering. At the early stage of the developmental process, PtoPIP1;1 OE Arabidopsis exhibited faster cell growth in both leaves and roots. The turgor pressure of plants was correspondingly increased in PtoPIP1;1 OE Arabidopsis, and the water status was changed. At the same time, the expression levels of flowering-related genes (CRY1, CRY2 and FCA) and hub genes in the regulatory networks underlying floral timing (FT and SOC1) were significantly upregulated in OE plants, while the floral repressor FLC gene was significantly downregulated. CONCLUSIONS: Taken together, the results of our study indicate that constitutive overexpression of PtoPIP1;1 in Arabidopsis accelerates bolting and flowering through faster cell growth in both the leaf and root at an early stage of the developmental process. The autonomous pathway of flowering regulation may be executed by monitoring developmental age. The increase in turgor and changes in water status with PtoPIP1;1 overexpression play a role in promoting cell growth.

Efficient Polysulfide Trapping and Conversion on N-Doped CoTe2 via Enhanced Dual-Anchoring Effect.

Polysulfide shuttling and sluggish sulfur redox kinetics hinder the cyclability and rate capability of lithium-sulfur (Li-S) batteries. The intrinsic redox kinetics of sulfur cathodes strongly depends on the interaction between catalysts and sulfur species. Herein, N-doped CoTe2 is proposed as an effective dual-anchoring electrocatalyst, which can simultaneously bind Li and S atoms in lithium polysulfides via ionic Te-Li/N-Li bonding and coordinate covalent Co-S bonding. The incorporated N not only serves as enhanced lithiophilic site, but also an agent to improve the sulfiphilicity of the Co site as revealed by a series of experimental and computational results. Benefiting from these superiorities, the use of N-doped CoTe2 as a catalytic interlayer enables efficient operation of Li-S batteries in terms of impressive rate capability of 758 mAh g-1 at 4 C and very low capacity decay of 0.021% per cycle over 1000 cycles. The material and strategy demonstrated in this work may open the door toward developing more advanced Li-S electrocatalysts.

The transcription factor KNAT2/6b mediates changes in plant architecture in response to drought via down-regulating GA20ox1 in Populus alba × P. glandulosa.

Plant architecture is genetically controlled, but is influenced by environmental factors. Plants have evolved adaptive mechanisms that allow changes in their architecture under stress, in which phytohormones play a central role. However, the gene regulators that connect growth and stress signals are rarely reported. Here, we report that a class I KNOX gene, PagKNAT2/6b, can directly inhibit the synthesis of gibberellin (GA), altering plant architecture and improving drought resistance in Populus. Expression of PagKNAT2/6b was significantly induced under drought conditions, and transgenic poplars overexpressing PagKNAT2/6b exhibited shorter internode length and smaller leaf size with short or even absent petioles. Interestingly, these transgenic plants showed improved drought resistance under both short- and long-term drought stress. Histological observations indicated that decreased internode length and leaf size were mainly caused by the inhibition of cell elongation and expansion. GA content was reduced, and the GA20-oxidase gene PagGA20ox1 was down-regulated in overexpressing plants. Expression of PagGA20ox1 was negatively related to that of PagKNAT2/6b under drought stress. ChIP and transient transcription activity assays revealed that PagGA20ox1 was directly targeted by PagKNAT2/6b. Therefore, this study provides evidence that PagKNAT2/6b mediates stress signals and changes in plant architecture via GA signaling by down-regulating PagGA20ox1.