High CO2 facilitates fatty acid biosynthesis and mitigates cellular oxidative stress caused by CAC2 dysfunction in Arabidopsis.

Increasing concentration of CO2 has significant impacts on many biological processes in plants, and its impact is closely associated with changes in the ratio of photosynthesis to photorespiration. Studies have reported that high CO2 can promote carbon fixing and alleviate plant oxidative damage in response to environmental stresses. However, the effect of high CO2 on fatty acid (FA) metabolism and cellular redox balance in FA-deficient plants is rarely reported. In this study, we identified a high-CO2 -requiring mutant cac2 through forward genetic screening. CAC2 encodes biotin carboxylase, which is one of the subunits of plastid acetyl-CoA carboxylase and participates in de novo FA biosynthesis. Null mutation of CAC2 is embryonic lethal. A point mutation of CAC2 in cac2 mutants produces severe defects in chloroplast development, plant growth and photosynthetic performance. These morphological and physiological defects were largely absent under high CO2 conditions. Metabolite analyses showed that FA contents in cac2-1 leaves were decreased, while photorespiratory metabolites, such as glycine and glycolate, did not significantly change. Meanwhile, cac2 exhibited higher reactive oxygen species (ROS) levels and mRNA expression of stress-responsive genes than the wild-type, indicating that cac2 plants may suffer oxidative stress under ambient CO2 conditions. Elevated CO2 significantly increased FA contents, especially C18:3-FA, and reduced ROS accumulation in cac2-1 leaves. We propose that stress mitigation by high CO2 in cac2 could be due to increased FA levels by promoting carbon assimilation, and the prevention of over-reduction due to decreased photorespiration.

Wounding induces a peroxisomal H2 O2 decrease via glycolate oxidase-catalase switch dependent on glutamate receptor-like channel-supported Ca2+ signaling in plants.

Sensing of environmental challenges, such as mechanical injury, by a single plant tissue results in the activation of systemic signaling, which attunes the plant's physiology and morphology for better survival and reproduction. As key signals, both calcium ions (Ca2+ ) and hydrogen peroxide (H2 O2 ) interplay with each other to mediate plant systemic signaling. However, the mechanisms underlying Ca2+ -H2 O2 crosstalk are not fully revealed. Our previous study showed that the interaction between glycolate oxidase and catalase, key enzymes of photorespiration, serves as a molecular switch (GC switch) to dynamically modulate photorespiratory H2 O2 fluctuations via metabolic channeling. In this study, we further demonstrate that local wounding induces a rapid shift of the GC switch to a more interactive state in systemic leaves, resulting in a sharp decrease in peroxisomal H2 O2 levels, in contrast to a simultaneous outburst of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived apoplastic H2 O2 . Moreover, the systemic response of the two processes depends on the transmission of Ca2+ signaling, mediated by glutamate-receptor-like Ca2+ channels 3.3 and 3.6. Mechanistically, by direct binding and/or indirect mediation by some potential biochemical sensors, peroxisomal Ca2+ regulates the GC switch states in situ, leading to changes in H2 O2 levels. Our findings provide new insights into the functions of photorespiratory H2 O2 in plant systemic acclimation and an optimized systemic H2 O2 signaling via spatiotemporal interplay between the GC switch and NADPH oxidases.

Shared and distinct reward neural mechanisms among patients with schizophrenia, major depressive disorder, and bipolar disorder: an effort-based functional imaging study.

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.

Two plastidic glycolate/glycerate translocator 1 isoforms function together to transport photorespiratory glycolate and glycerate in rice chloroplasts.

The photorespiratory pathway is highly compartmentalized. As such, metabolite shuttles between organelles are critical to ensure efficient photorespiratory carbon flux. Arabidopsis plastidic glycolate/glycerate translocator 1 (PLGG1) has been reported as a key chloroplastic glycolate/glycerate transporter. Two homologous genes, OsPLGG1a and OsPLGG1b, have been identified in the rice genome, although their distinct functions and relationships remain unknown. Herein, our analysis of exogenous expression in oocytes and yeast shows that both OsPLGG1a and OsPLGG1b have the ability to transport glycolate and glycerate. Furthermore, we demonstrate in planta that the perturbation of OsPLGG1a or OsPLGG1b expression leads to extensive accumulation of photorespiratory metabolites, especially glycolate and glycerate. Under ambient CO2 conditions, loss-of-function osplgg1a or osplgg1b mutant plants exhibited significant decreases in photosynthesis efficiency, starch accumulation, plant height, and crop productivity. These morphological defects were almost entirely recovered when the mutant plants were grown under elevated CO2 conditions. In contrast to osplgg1a, osplgg1b mutant alleles produced a mild photorespiratory phenotype and had reduced accumulation of photorespiratory metabolites. Subcellular localization analysis showed that OsPLGG1a and OsPLGG1b are located in the inner and outer membranes of the chloroplast envelope, respectively. In vitro and in vivo experiments revealed that OsPLGG1a and OsPLGG1b have a direct interaction. Our results indicate that both OsPLGG1a and OsPLGG1b are chloroplastic glycolate/glycerate transporters required for photorespiratory metabolism and plant growth, and that they may function as a singular complex.

FAR-RED ELONGATED HYPOCOTYL3 activates SEPALLATA2 but inhibits CLAVATA3 to regulate meristem determinacy and maintenance in Arabidopsis.

Plant meristems are responsible for the generation of all plant tissues and organs. Here we show that the transcription factor (TF) FAR-RED ELONGATED HYPOCOTYL3 (FHY3) plays an important role in both floral meristem (FM) determinacy and shoot apical meristem maintenance in Arabidopsis, in addition to its well-known multifaceted roles in plant growth and development during the vegetative stage. Through genetic analyses, we show that WUSCHEL (WUS) and CLAVATA3 (CLV3), two central players in the establishment and maintenance of meristems, are epistatic to FHY3 Using genome-wide ChIP-seq and RNA-seq data, we identify hundreds of FHY3 target genes in flowers and find that FHY3 mainly acts as a transcriptional repressor in flower development, in contrast to its transcriptional activator role in seedlings. Binding motif-enrichment analyses indicate that FHY3 may coregulate flower development with three flower-specific MADS-domain TFs and four basic helix-loop-helix TFs that are involved in photomorphogenesis. We further demonstrate that CLV3, SEPALLATA1 (SEP1), and SEP2 are FHY3 target genes. In shoot apical meristem, FHY3 directly represses CLV3, which consequently regulates WUS to maintain the stem cell pool. Intriguingly, CLV3 expression did not change significantly in fhy3 and phytochrome B mutants before and after light treatment, indicating that FHY3 and phytochrome B are involved in light-regulated meristem activity. In FM, FHY3 directly represses CLV3, but activates SEP2, to ultimately promote FM determinacy. Taken together, our results reveal insights into the mechanisms of meristem maintenance and determinacy, and illustrate how the roles of a single TF may vary in different organs and developmental stages.

EXPORTIN 1A prevents transgene silencing in Arabidopsis by modulating nucleo-cytoplasmic partitioning of HDA6.

In eukaryotic cells, transport of macromolecules across the nuclear envelope is an essential process that ensures rapid exchange of cellular components, including protein and RNA molecules. Chromatin regulators involved in epigenetic control are among the molecules exported across the nuclear envelope, but the significance of this nucleo-cytoplasmic trafficking is not well understood. Here, we use a forward screen to isolate XPO1A (a nuclear export receptor in Arabidopsis) as an anti-silencing factor that protects transgenes from transcriptional silencing. Loss-of-function of XPO1A leads to locus-specific DNA hypermethylation at transgene promoters and some endogenous loci. We found that XPO1A directly interacts with histone deacetylase HDA6 in vivo and that the xpo1a mutation causes increased nuclear retention of HDA6 protein and results in reduced histone acetylation and enhanced transgene silencing. Our results reveal a new mechanism of epigenetic regulation through the modulation of XPO1A-dependent nucleo-cytoplasm partitioning of a chromatin regulator.

Impairment of FtsHi5 Function Affects Cellular Redox Balance and Photorespiratory Metabolism in Arabidopsis.

Photorespiration is an essential process for plant photosynthesis, development and growth in aerobic conditions. Recent studies have shown that photorespiration is an open system integrated with the plant primary metabolism network and intracellular redox systems, though the mechanisms of regulating photorespiration are far from clear. Through a forward genetic method, we identified a photorespiratory mutant pr1 (photorespiratory related 1), which produced a chlorotic and smaller photorespiratory growth phenotype with decreased chlorophyll content and accumulation of glycine and serine in ambient air. Morphological and physiological defects in pr1 plants can be largely abolished under elevated CO2 conditions. Genetic mapping and complementation confirmed that PR1 encodes an FtsH (Filamentation temperature-sensitive H)-like protein, FtsHi5. Reduced FtsHi5 expression in DEX-induced RNAi transgenic plants produced a similar growth phenotype with pr1 (ftsHi5-1). Transcriptome analysis suggested a changed expression pattern of redox-related genes and an increased expression of senescence-related genes in DEX: RNAi-FtsHi5 seedlings. Together with the observation that decreased accumulation of D1 and D2 proteins of photosystem II (PSII) and over-accumulation of reactive oxygen species (ROS) in ftsHi5 mutants, we hypothesize that FtsHi5 functions in maintaining the cellular redox balance and thus regulates photorespiratory metabolism.

[Transrectal ultrasound conductance-guided administration of traditional Chinese medicine for histological prostatitis in men with small-size BPH and LUTS after TURP].

OBJECTIVE: To investigate the effects of transrectal ultrasound conductance (TRUSC)-guided administration of traditional Chinese medicine on histological prostatitis in men with small-size BPH and low urinary tract symptoms (LUTS) after transurethral resection of the prostate (TURP). METHODS: This study included 167 BPH patients without surgical contraindications. We randomized the patients into an experimental group (n = 84) and a control group (n = 83), with no statistically significant differences between the two groups in age, prostate volume, International Prostate Symptom Score (IPSS), and quality of life (QoL) (P >0.05). The patients of the experimental group received TRUSC-guided administration of traditional Chinese medicine, qd, for 7 days before TURP, while those of the control group underwent TURP only. After treatment, we compared the results of postoperative pathological examination of the prostate tissue, the histological grade of inflammation, IPSS, and QoL scores between the two groups of patients. RESULTS: In the experimental group, there were 12 cases of non-inflammation (14.3%), 43 cases of mild inflammation (51.2%), 28 cases of moderate inflammation (33.3%), and 1 case of severe inflammation (1.2%), as compared with 8 cases of non-inflammation (9.6%), 28 cases of mild inflammation (33.7%), 45 cases of moderate inflammation (51.8%), and 2 cases of severe inflammation (2.4%) in the control group (P <0.05). Compared with the baseline, both the experimental and control groups showed significant improvement at 4 weeks after surgery in IPSS (22.20±4.14 vs 4.26±2.64 and 23.05±4.11 vs 7.02±4.15, P <0.05) and QoL scores (4.33±0.83 vs 1.25±1.64 and 4.25±0.91 vs 2.05±1.95, P <0.05). CONCLUSIONS: TRUSC-guided administration of traditional Chinese medicine can significantly alleviate histological inflammation and improve QoL in men with small-size BPH and LUTS after TURP.

Endovascular treatment of cerebellar arteriovenous malformations: management of associated aneurysms first or later.

The purpose of this study was to determine the safety and effectiveness of cerebellar arteriovenous malformations (AVMs) embolization and find out the suitable methods to manage associated aneurysms. Medical records of all patients between 1997 and 2014 with a diagnosis of cerebellar AVMs were retrospectively reviewed. Univariable and multivariable logistic analysis were used to assess AVMs characteristics to calculate for the risk of hemorrhage. Endovascular treatment was the main treatment measure to manage the AVMs and associated aneurysms. Of 142 patients, 115 (81.0 %) presented with hemorrhage and 42 (29.6 %) with associated aneurysms. A significant association with cerebellar AVMs hemorrhage was found for small size, prenidal aneurysms, and deep venous drainage in the univariable and multivariable analysis. Associated aneurysms were treated firstly in 41 patients except for 1 patient with 2 prenidal and 2 intranidal aneurysms. The special case was dealt with AVMs and 2 intranidal aneurysms first and angiography showed that the 2 prenidal associated aneurysms disappeared with time. Hemorrhage appeared in 13/142 patients (9.2 %) during the follow-up period, none of which was with associated aneurysms. Endovascular treatment can be a feasible way for treating cerebellar AVMs. Intranidal associated aneurysms should be treated first. Prenidal associated aneurysms can be treated later depending on the angioarchitecture of AVMs.

RNA-binding protein regulates plant DNA methylation by controlling mRNA processing at the intronic heterochromatin-containing gene IBM1.

DNA methylation-dependent heterochromatin formation is a conserved mechanism of epigenetic silencing of transposons and other repeat elements in many higher eukaryotes. Genes adjacent to repetitive elements are often also subjected to this epigenetic silencing. Consequently, plants have evolved antisilencing mechanisms such as active DNA demethylation mediated by the REPRESSOR OF SILENCING 1 (ROS1) family of 5-methylcytosine DNA glycosylases to protect these genes from silencing. Some transposons and other repeat elements have found residence in the introns of genes. It is unclear how these intronic repeat elements-containing genes are regulated. We report here the identification of ANTI-SILENCING 1 (ASI1), a bromo-adjacent homology domain and RNA recognition motif-containing protein, from a forward genetic screen for cellular antisilencing factors in Arabidopsis thaliana. ASI1 is required to prevent promoter DNA hypermethylation and transcriptional silencing of some transgenes. Genome-wide DNA methylation analysis reveals that ASI1 has a similar role to that of the histone H3K9 demethylase INCREASE IN BONSAI METHYLATION 1 (IBM1) in preventing CHG methylation in the bodies of thousands of genes. We found that ASI1 is an RNA-binding protein and ensures the proper expression of IBM1 full-length transcript by associating with an intronic heterochromatic repeat element of IBM1. Through mRNA sequencing, we identified many genes containing intronic transposon elements that require ASI1 for proper expression. Our results suggest that ASI1 associates with intronic heterochromatin and binds the gene transcripts to promote their 3' distal polyadenylation. The study thus reveals a unique mechanism by which higher eukaryotes deal with the collateral effect of silencing intronic repeat elements.

The inhibitory effect of mesenchymal stem cell on blood-brain barrier disruption following intracerebral hemorrhage in rats: contribution of TSG-6.

BACKGROUND: Mesenchymal stem cells (MSCs) are well known having beneficial effects on intracerebral hemorrhage (ICH) in previous studies. The therapeutic mechanisms are mainly to investigate proliferation, differentiation, and immunomodulation. However, few studies have used MSCs to treat blood-brain barrier (BBB) leakage after ICH. The influence of MSCs on the BBB and its related mechanisms were investigated when MSCs were transplanted into rat ICH model in this study. METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into sham-operated group, PBS-treated (ICH + PBS) group, and MSC-treated (ICH + MSC) group. ICH was induced by injection of IV collagenase into the rats' brains. MSCs were transplanted intravenously into the rats 2 h after ICH induction in MSC-treated group. The following factors were compared: inflammation, apoptosis, behavioral changes, inducible nitric oxide synthase (iNOS), matrix metalloproteinase 9 (MMP-9), peroxynitrite (ONOO(-)), endothelial integrity, brain edema content, BBB leakage, TNF-α stimulated gene/protein 6 (TSG-6), and nuclear factor-κB (NF-κB) signaling pathway. RESULTS: In the ICH + MSC group, MSCs decreased the levels of proinflammatory cytokines and apoptosis, downregulated the density of microglia/macrophages and neutrophil infiltration at the ICH site, reduced the levels of iNOS and MMP-9, attenuated ONOO(-) formation, and increased the levels of zonula occludens-1 (ZO-1) and claudin-5. MSCs also improved the degree of brain edema and BBB leakage. The protective effect of MSCs on the BBB in ICH rats was possibly invoked by increased expression of TSG-6, which may have suppressed activation of the NF-κB signaling pathway. The levels of iNOS and ONOO(-), which played an important role in BBB disruption, decreased due to the inhibitory effects of TSG-6 on the NF-κB signaling pathway. CONCLUSIONS: Our results demonstrated that intravenous transplantation of MSCs decreased the levels of ONOO(-) and degree of BBB leakage and improved neurological recovery in a rat ICH model. This strategy may provide a new insight for future therapies that aim to prevent breakdown of the BBB in patients with ICH and eventually offer therapeutic options for ICH.

AtDsPTP1 acts as a negative regulator in osmotic stress signalling during Arabidopsis seed germination and seedling establishment.

Dual-specificity protein phosphatases (DsPTPs) target both tyrosine and serine/threonine residues and play roles in plant growth and development. We have characterized an Arabidopsis mutant, dsptp1, which shows a higher seed germination rate and better root elongation under osmotic stress than the wild type. By contrast, its overexpression line, DsPTP1-OE, shows inhibited seed germination and root elongation; and its complemented line, DsPTP1-Com, resembles the wild type and rescues DsPTP1-OE under osmotic stress. Expression of AtDsPTP1 is enhanced by osmotic stress in seed coats, bases of rosette leaves, and roots. Compared with the wild type, the dsptp1 mutant shows increased proline accumulation, reduced malondialdehyde (MDA) content and ion leakage, and enhanced antioxidant enzyme activity in response to osmotic stress. AtDsPTP1 regulates the transcript levels of various dehydration-responsive genes under osmotic stress. Abscisic acid (ABA) accumulation in dsptp1 under osmotic stress is reduced with reduced expression of the ABA-biosynthesis gene NCED3 and increased expression of the ABA-catabolism gene CYP707A4. AtDsPTP1 also regulates the expression of key components in the ABA-signalling pathway. In conclusion, AtDsPTP1 regulates ABA accumulation, and acts as a negative regulator in osmotic stress signalling during Arabidospsis seed germination and seedling establishment.

Predictors of Favorable Outcome of Intracranial Basilar Dissecting Aneurysm.

BACKGROUND: Management of intracranial basilar dissecting aneurysms has been controversial and challenging, and surgical and conservative treatments usually have a bad prognosis. Our study aimed at evaluating the outcomes of endovascular treatment for these lesions and exploring the predictors of favorable outcome. METHODS: We retrospectively reviewed 50 consecutive patients with basilar dissecting aneurysms from January 2006 to January 2013. Twenty-four patients underwent stent-assisted coiling whereas 26 patients underwent conservative treatment. Follow-up outcomes were evaluated using modified Rankin Scale (mRS) score. RESULTS: Of the patients treated with stent-assisted coiling, 20 patients had a favorable outcome (mRS score, 0-1), post-treatment recurrence occurred in 3 patients, 1 had rebleeding, and 2 had no rebleeding. Of the patients treated with conservative therapy (observation or anticoagulation), 10 patients had an unfavorable outcome, 2 patients with ruptured aneurysms developed rebleeding, and 8 patients had poor outcome because of infarct progression. Stent-assisted coiling group had a more favorable outcome than the conservatively treated group (83.3% versus 55.2%, P = .019). Initial complete obliteration was related to the favorable outcome in endovascular-treated group (P = .042). Stent placement was the only independent predictor of favorable outcome in the logistic regression analysis (P = .030; odds ratio = 5.828; 95% confidence interval, 1.192-28.503). CONCLUSIONS: Patients with basilar artery dissecting aneurysms treated with stent-assisted coiling had a more favorable outcome than the conservatively treated patients. Stent placement and initial complete occlusion were the favorable factors in patients with basilar dissecting aneurysm.

Endovascular Treatment of Dissecting Aneurysms of the Posterior Inferior Cerebellar Artery and Predictors of Outcome.

BACKGROUND: Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) are rare lesions, which carry high risk of rebleeding and mortality. However, the existing literature concerning predictors of outcome after endovascular treatment is limited and controversial. Our present study retrospectively reviewed and analyzed the clinical outcome of endovascular treatment-ruptured PICA-dissecting aneurysms and explored the predictors of outcome. METHODS: We retrospectively reviewed 17 consecutive patients with ruptured PICA dissecting aneurysms that underwent endovascular treatment from January 2003 to January 2014. Nine patients underwent selective coiling, whereas 7 patients underwent parent artery occlusion and 1 patient underwent stent-assisted coiling. Follow-up outcomes were evaluated using the modified Rankin Scale. The clinical outcomes of patients were categorized as favorable (modified Rankin Scale [mRS] score 0-1) or unfavorable (mRS score 2-6). RESULTS: Favorable outcomes (mRS score 0-1) were obtained in 13 of 17 patients. Post-treatment recurrence occurred in 1 patient with selective coiling in the 15-month follow-up, and the patient received stent-assisted coiling. The only patients with stent-assisted coiling developed PICA occlusion during follow-up. Aneurysm located in distal segment usually presented with intraventricular hemorrhage (P = .015). Hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks) were associated with unfavorable outcome. CONCLUSIONS: Endovascular treatment of isolated dissecting aneurysm of PICA had excellent clinical outcomes, hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks), which were associated with unfavorable outcome. Long-term follow-ups are necessary to provide stronger conclusions.

Copper suppresses abscisic acid catabolism and catalase activity, and inhibits seed germination of rice.

Although copper (Cu) is an essential micronutrient for plants, a slight excess of Cu in soil can be harmful to plants. Unfortunately, Cu contamination is a growing problem all over the world due to human activities, and poses a soil stress to plant development. As one of the most important biological processes, seed germination is sensitive to Cu stress. However, little is known about the mechanism of Cu-induced inhibition of seed germination. In the present study, we investigated the relationship between Cu and ABA which is the predominant regulator of seed germination. Cu at a concentration of 30 µM effectively inhibited germination of rice caryopsis. ABA content in germinating seeds under copper stress was also higher than that under control conditions. Quantitative real-time PCR (qRT-PCR) revealed that Cu treatment reduced the expression of OsABA8ox2, a key gene of ABA catabolism in rice seeds. In addition, both malondialdehyde (MDA) and H2O2 contents were increased by Cu stress in the germinating seeds. Antioxidant enzyme assays revealed that only catalase activity was reduced by excess Cu, which was consistent with the mRNA profile of OsCATa during seed germination under Cu stress. Together, our results demonstrate that suppression of ABA catabolism and catalase (CAT) activity by excess Cu leads to the inhibition of seed germination of rice.

A fully automatic deep learning-based method for segmenting regions of interest and predicting renal function in pediatric dynamic renal scintigraphy.

OBJECTIVE: Accurate delineation of renal regions of interest (ROIs) is critical for the assessment of renal function in pediatric dynamic renal scintigraphy (DRS). The purpose of this study was to develop and evaluate a deep learning (DL) model that can fully automatically delineate renal ROIs and calculate renal function in pediatric 99mTechnetium-ethylenedicysteine (99mTc-EC) DRS. METHODS: This study retrospectively analyzed 1,283 pediatric DRS data at a single center from January to December 2018. These patients were divided into training set (n = 1027), validation set (n = 128), and testing set (n = 128). A fully automatic segmentation of ROIs (FASR) model was developed and evaluated. The pixel values of the automatically segmented ROIs were calculated to predict renal blood perfusion rate (BPR) and differential renal function (DRF). Precision, recall rate, intersection over union (IOU), and Dice similarity coefficient (DSC) were used to evaluate the performance of FASR model. Intraclass correlation (ICC) and Pearson correlation analysis were used to compare the consistency of automatic and manual method in assessing the renal function parameters in the testing set. RESULTS: The FASR model achieved a precision of 0.88, recall rate of 0.94, IOU of 0.83, and DSC of 0.91. In the testing set, the r values of BPR and DRF calculated by the two methods were 0.94 (P < 0.01) and 0.97 (P < 0.01), and the ICCs (95% confidence interval CI) were 0.94 (0.90-0.96) and 0.94 (0.91-0.96). CONCLUSION: We propose a reliable and stable DL model that can fully automatically segment ROIs and accurately predict renal function in pediatric 99mTc-EC DRS.

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Enzymatically active Rho and Rac small-GTPases are involved in the establishment of the vacuolar membrane after Toxoplasma gondii invasion of host cells.

BACKGROUND: GTPases are the family of hydrolases that bind and hydrolyze guanosine triphosphate. The large Immunity-related GTPases and the small GTPase ADP-ribosylation factor-6 in host cells are known to accumulate on the parasitophorous vacuole membrane (PVM) of Toxoplasma gondii and play critical roles in this parasite infection, but these GTPases cannot explain the full extent of infection. RESULTS: In this research, RhoA and Rac1 GTPases from the host cell were found to accumulate on the PVM regardless of the virulence of the T. gondii strains after T. gondii invasion, and this accumulation was dependent on their GTPase activity. The real-time micrography of T. gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA showed that this GTPase was recruited to the PVM at the very beginning of the invasion through the host cell membrane or from the cytosol. Host cell RhoA and Rac1 were also activated after T. gondii tachyzoites invasion, which was needed for host cell cytoskeleton reorganization to facilitate intracellular pathogens invasion. The decisive domains for the RhoA accumulation on the PVM included the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which were related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited CFP-RhoA on the PVM could not be activated by epithelial growth factor (EGF) and no translocation was observed, unlike the unassociated RhoA in the host cell cytosol that migrated to the cell membrane towards the EGF activation spot. This result supported the hypothesis that the recruited RhoA or Rac1 on the PVM were in the GTP-bound active form. Wild-type RhoA or Rac1 overexpressed cells had almost the same infection rates by T. gondii as the mock-treated cells, while RhoA-N19 or Rac1-N17 transfected cells and RhoA, Rac1 or RhoA + Rac1 siRNA-treated cells showed significantly diminished infection rates compared to mock cells. CONCLUSIONS: The accumulation of the RhoA and Rac1 on the PVM and the requisite of their normal GTPase activity for efficient invasion implied their involvement and function in T. gondii invasion.

JMJ28 guides sequence-specific targeting of ATX1/2-containing COMPASS-like complex in Arabidopsis.

Despite extensive investigations in mammals and yeasts, the importance and specificity of COMPASS-like complex, which catalyzes histone 3 lysine 4 methylation (H3K4me), are not fully understood in plants. Here, we report that JMJ28, a Jumonji C domain-containing protein in Arabidopsis, recognizes specific DNA motifs through a plant-specific WRC domain and acts as an interacting factor to guide the chromatin targeting of ATX1/2-containing COMPASS-like complex. JMJ28 associates with COMPASS-like complex in vivo via direct interaction with RBL. The DNA-binding activity of JMJ28 is essential for both the targeting specificity of ATX1/2-COMPASS and the deposition of H3K4me at specific loci but exhibit functional redundancy with alternative COMPASS-like complexes at other loci. Finally, we demonstrate that JMJ28 is a negative regulator of plant immunity. In summary, our findings reveal a plant-specific recruitment mechanism of COMPASS-like complex. These findings help to gain deeper insights into the regulatory mechanism of COMPASS-like complex in plants.

Comparisons of facial emotion recognition in different social contexts among patients with schizophrenia, major depressive disorder and bipolar disorder.

BACKGROUND: Previous studies have found that patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD) all have facial emotion recognition deficits, but the differences and similarities of these deficits in the three groups of patients under different social interaction situations are not clear. The present study aims to compare the ability of facial emotion recognition in three different conversation situations from a cross-diagnostic perspective. METHODS: Thirty-three participants with SCZ, 35 participants with MDD, and 30 participants with BD were recruited, along with 31 healthy controls. A computer-based task was given to assess the ability of Facial Emotion Categorization (FEC) under three different conversational situations (praise, blame, and inquiry). RESULTS: In the "praise" situation, patients with SCZ, MDD and BD were all slower to recognize anger emotion than the healthy controls. In all three clinical groups, patients with SCZ recognized angry faces faster than those with MDD and BD on a continuum from happy faces to angry faces in the "inquiry" situation, while no significant difference was found in the latter two groups. In addition, no significant defect was found in the percentage and threshold of angry face recognition in all three patient groups. CONCLUSIONS: Our findings indicate that patients with SCZ, MDD, and BD share both common and distinct deficits in facial emotion recognition during social interactions, which may be beneficial for early screening and precise intervention for these mental disorders.