SNAC1-OsERF103-OsSDG705 module mediates drought response in rice.

Drought stress profoundly hampers both plant growth and crop yield. To combat this, plants have evolved intricate transcriptional regulation mechanisms as a pivotal strategy. Through a genetic screening with rice genome-scale mutagenesis pool under drought stress, we identified an APETALA2/Ethylene Responsive Factor, namely OsERF103, positively responds to drought tolerance in rice. Combining chromatin immunoprecipitation sequencing and RNA sequencing analyses, we pinpointed c. 1000 genes directly influenced by OsERF103. Further results revealed that OsERF103 interacts with Stress-responsive NAC1 (SNAC1), a positive regulator of drought tolerance in rice, to synergistically regulate the expression of key drought-related genes, such as OsbZIP23. Moreover, we found that OsERF103 recruits a Su(var)3-9,enhancer of zeste and trithorax-domain group protein 705, which encodes a histone 3 lysine 4 (H3K4)-specific methyltransferase to specifically affect the deposition of H3K4me3 at loci like OsbZIP23 and other genes linked to dehydration responses. Additionally, the natural alleles of OsERF103 are selected during the domestication of both indica and japonica rice varieties and exhibit significant geographic distribution. Collectively, our findings have unfurled a comprehensive mechanistic framework underlying the OsERF103-mediated cascade regulation of drought response. This discovery not only enhances our understanding of drought signaling but also presents a promising avenue for the genetic improvement of drought-tolerant rice cultivars.

Effect of different implant angulations on the biomechanical performance of prosthetic screws in two implant-supported, screw-retained prostheses: A numerical and experimental study.

STATEMENT OF PROBLEM: A mesiodistal angle frequently forms between 2 splinted implant-supported, screw-retained fixed dental prostheses (TIS-FDPs). Mechanical complications commonly occur in prosthetic screws. Studies regarding the effect of the degree of implant angulation on the biomechanical performance of prosthetic screws in TIS-FDPs are sparse. PURPOSE: The purpose of this numerical and experimental study was to investigate the effects of different implant angulations on the biomechanical performance, including stress distribution, stability of the screw joint, and surface morphology change of the prosthetic screws in TIS-FDPs. MATERIAL AND METHODS: TIS-FDPs were classified into 4 groups: 0, 10, 20, and 30 degrees based on the degree of mesiodistal angle between the long axes of the 2 implants. In the finite element analysis (FEA), 4 series of 3D models were constructed and loaded with simulated occlusal forces. The von Mises stresses and rotational angles of the prosthetic screws were then calculated. In the mechanical test, each group of 5 TIS-FDPs with 10 prosthetic screws was tested under 1 million loading cycles by using a universal testing machine. The removal torque values (RTVs) and the surface roughness of the prosthetic screws were measured after cyclic loading. The normality of the outcome variables was assessed by the Shapiro-Wilk test. Analysis of variance and the Kruskal-Wallis test were used for further analysis (α=.05). RESULTS: The FEA results showed that the von Mises stresses of the prosthetic screws were concentrated in the first screw thread crest engaged with the abutment, and the maximum values of the threads and the rotation angles of the prosthetic screws increased in the 2-implant mesiodistal angulation from 0 to 30 degrees. The mechanical tests showed that the RTVs of the prosthetic screws in each group were not significantly different after 1 million loading cycles (P=.107). The surface roughness of the crest of the first 2 threads of the prosthetic screws in the 30-degree group changed significantly compared with those in the other groups. CONCLUSIONS: When TIS-FDPs were delivered, larger angulations of the 2 splinted implants seemed to increase the stress concentrated on the crest of the first engaged thread and the rotation angles of the prosthetic screws. After 1 million loading cycles, significant surface adhesive wear was identified on the crest of the first 2 threads of the prosthetic screws in the 30-degree group compared with groups with a smaller angulation.

The OsbHLH002/OsICE1-OSH1 module orchestrates secondary cell wall formation in rice.

Transcriptional regulation of secondary cell wall (SCW) formation is strictly controlled by a complex network of transcription factors in vascular plants and has been shown to be mediated by a group of NAC master switches. In this study, we show that in a bHLH transcription factor, OsbHLH002/OsICE1, its loss-of-function mutant displays a lodging phenotype. Further results show that OsbHLH002 and Oryza sativa homeobox1 (OSH1) interact and share a set of common targets. In addition, the DELLA protein SLENDER RICE1, rice ortholog of KNOTTED ARABIDOPSIS THALIANA7, and OsNAC31 interact with OsbHLH002 and OSH1 and regulate their binding capacity on OsMYB61, a key regulatory factor in SCW development. Collectively, our results indicate OsbHLH002 and OSH1 as key regulators in SCW formation and shed light on molecular mechanisms of how active and repressive factors precisely orchestrate SCW synthesis in rice, which may provide a strategy for manipulating plant biomass production.

Dietary palmitoleic acid reprograms gut microbiota and improves biological therapy against colitis.

Magnitude and diversity of gut microbiota and metabolic systems are critical in shaping human health and diseases, but it remains largely unclear how complex metabolites may selectively regulate gut microbiota and determine health and diseases. Here, we show that failures or compromised effects of anti-TNF-α therapy in inflammatory bowel diseases (IBD) patients were correlated with intestinal dysbacteriosis with more pro-inflammatory bacteria, extensive unresolved inflammation, failed mucosal repairment, and aberrant lipid metabolism, particularly lower levels of palmitoleic acid (POA). Dietary POA repaired gut mucosal barriers, reduced inflammatory cell infiltrations and expressions of TNF-α and IL-6, and improved efficacy of anti-TNF-α therapy in both acute and chronic IBD mouse models. Ex vivo treatment with POA in cultured inflamed colon tissues derived from Crohn's disease (CD) patients reduced pro-inflammatory signaling/cytokines and conferred appreciable tissue repairment. Mechanistically, POA significantly upregulated the transcriptional signatures of cell division and biosynthetic process of Akkermansia muciniphila, selectively increased the growth and abundance of Akkermansia muciniphila in gut microbiota, and further reprogrammed the composition and structures of gut microbiota. Oral transfer of such POA-reprogrammed, but not control, gut microbiota induced better protection against colitis in anti-TNF-α mAb-treated recipient mice, and co-administration of POA with Akkermansia muciniphila showed significant synergistic protections against colitis in mice. Collectively, this work not only reveals the critical importance of POA as a polyfunctional molecular force to shape the magnitude and diversity of gut microbiota and therefore promote the intestinal homeostasis, but also implicates a new potential therapeutic strategy against intestinal or abenteric inflammatory diseases.

A Machine Learning Model Based on GRU and LSTM to Predict the Environmental Parameters in a Layer House, Taking CO2 Concentration as an Example.

In a layer house, the CO2 (carbon dioxide) concentration above the upper limit can cause the oxygen concentration to be below the lower limit suitable for poultry. This leads to chronic CO2 poisoning in layers, which manifests as listlessness, reduced appetite, weak constitution, decreased production performance, and weakened resistance to disease. Regulating ventilation may ensure a suitable CO2 concentration in layer houses. Predicting the changes in CO2 concentration and regulating the CO2 concentration in advance are key to ensuring healthy large-scale breeding of layers. In recent years, machine learning and deep learning methods have been increasingly applied to this field. A CO2 prediction model for layer house is proposed based on a GRU (gated recurrent unit) and LSTM (long short-term memory). The temperature, humidity, and CO2 were determined as inputs to the model by the correlation coefficient. The datasets of the experimental layer house were continuously measured during June-July 2023, using a self-developed environmental monitor, and the monitored data were used as samples for model inputs. There were 22,000 time series data in the datasets. In this study, multivariate time series data were standardized via data pre-processing to improve model training. GRU and LSTM models were constructed. The models were trained using a training set. Then, these trained models were used to provide predictions on a test set. The prediction errors were calculated using the true values of the test set and the predicted values provided by the models. To test the performance of the model and accuracy of the predictions, predictions were made for different numbers of datasets. The results demonstrated that the combined prediction model had good generalization, stability, and convergence with high prediction accuracy. Due to the structure of the model, the stability of the LSTM model was higher than that of the GRU model, and its prediction accuracy and speed were lower than those of the GRU model. When the datasets of the GRU model were 15,000 to 17,000, The MAE of the GRU was 70.8077 to 126.7029 ppm, and the prediction time of the GRU is 16 to 24 ms. When the LSTM model's datasets were 15,000-20,000, the MAE of LSTM was 78.8596 to 136.0896 ppm, and the prediction time of the GRU was 17 to 26 ms.

MicroRNA-31 mediated by interferon regulatory factor 7 signaling facilitates control of Mycobacterium tuberculosis infection.

Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection.

The OsFTIP6-OsHB22-OsMYBR57 module regulates drought response in rice.

Plants have evolved a sophisticated set of mechanisms to adapt to drought stress. Transcription factors play crucial roles in plant responses to various environmental stimuli by modulating the expression of numerous stress-responsive genes. However, how the crosstalk between different transcription factor families orchestrates initiation of the key transcriptional network and the role of posttranscriptional modification of transcription factors, especially in cellular localization/trafficking in response to stress in rice, remain still largely unknown. In this study, we isolated an Osmybr57 mutant that displays a drought-sensitive phenotype through a genetic screen for drought stress sensitivity. We found that OsMYBR57, an MYB-related protein, directly regulates the expression of several key drought-related OsbZIPs in response to drought treatment. Further studies revealed that OsMYBR57 interacts with a homeodomain transcription factor, OsHB22, which also plays a positive role in drought signaling. We further demonstrate that OsFTIP6 interacts with OsHB22 and promotes the nucleocytoplasmic translocation of OsHB22 into the nucleus, where OsHB22 cooperates with OsMYBR57 to regulate the expression of drought-responsive genes. Our findings have revealed a mechanistic framework underlying the OsFTIP6-OsHB22-OsMYBR57 module-mediated regulation of drought response in rice. The OsFTIP6-mediated OsHB22 nucleocytoplasmic shuttling and OsMYBR57-OsHB22 regulation of OsbZIP transcription ensure precise control of expression of OsLEA3 and Rab21, and thereby regulate the response to water deficiency in rice.

The tetratricopeptide repeat protein OsTPR075 promotes heading by regulating florigen transport in rice.

Rice (Oryza sativa) is one of the most important crops worldwide. Heading date is a vital agronomic trait that influences rice yield and adaption to local conditions. Hd3a, a proposed florigen that primarily functions under short-day (SD) conditions, is a mobile flowering signal that promotes the floral transition in rice. Nonetheless, how Hd3a is transported from leaves to the shoot apical meristem (SAM) under SDs remains elusive. Here, we report that FT-INTERACTING PROTEIN9 (OsFTIP9) specifically regulates rice flowering time under SDs by facilitating Hd3a transport from companion cells (CCs) to sieve elements (SEs). Furthermore, we show that the tetratricopeptide repeat (TPR) protein OsTPR075 interacts with both OsFTIP9 and OsFTIP1 and strengthens their respective interactions with Hd3a and the florigen RICE FLOWERING LOCUS T1 (RFT1). This in turn affects the trafficking of Hd3a and RFT1 to the SAM, thus regulating flowering time under SDs and long-day conditions, respectively. Our findings suggest that florigen transport in rice is mediated by different OsFTIPs under different photoperiods and those interactions between OsTPR075 and OsFTIPs are essential for mediating florigen movement from leaves to the SAM.

Efficacy and safety of omalizumab in Chinese patients with anti-histamine refractory chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous development of wheals, itching, and/or angioedema, for ≥6 weeks. In China, non-sedating H1-antihistamines (H1AH) are the recommended first-line treatment, with escalation up to 4× the standard dose in symptomatic patients to achieve control. Treatment options for Chinese patients who remain symptomatic on H1AH treatment are limited. This 20-week randomized, double blind, placebo-controlled, parallel-group study investigated the efficacy and safety of omalizumab as an add-on therapy for the treatment of patients with CSU who remained symptomatic despite H1AH treatment in China. Adult patients (N = 418) diagnosed with refractory CSU for ≥6 months were randomized (2:2:1) to receive omalizumab 300 mg (OMA300), omalizumab 150 mg (OMA150) or placebo, subcutaneously, every 4 weeks. Primary outcome was change from baseline to week 12 in weekly itch severity score (ISS7). Safety was assessed by rates of adverse events (AEs). Demographic and disease characteristics at baseline were comparable across treatment groups. At week 12, statistically significant greater decreases from baseline were observed in ISS7 with OMA300 (least square mean difference [LSM]: -4.23; 95% confidence interval [CI]: -5.70, -2.77; p < 0.001) and OMA150 (LSM: -3.79; 95% CI: -5.24, -2.33; p < 0.001) versus placebo. Incidence of treatment-emergent AEs over 20 weeks was slightly higher with OMA300 (71.3%) compared to OMA150 and placebo groups (64.7% and 63.9%, respectively). The incidences of serious AEs were balanced between groups. This study demonstrated the efficacy and safety of omalizumab in Chinese adult patients with CSU who remained symptomatic despite H1AH therapy.

Diversely C8-functionalized adenine nucleosides via their underexplored carboxaldehydes.

The potentially versatile N-unprotected 8-formyl derivatives of adenosine and 2'-deoxyadenosine are highly underexploited for C8 modifications of these nucleosides. Only in situ formation of 8-formyladenosine is known and a single application of an N-benzoyl derivative has been reported. On the other hand, 8-formyl-2'-deoxyadenosine and its applications remain unknown. Herein, we report straightforward, scalable syntheses of both N-unprotected 8-formyladenine nucleoside derivatives, and demonstrate broad diversification at the C8 position by hydroxymethylation, azidation, CuAAC ligation, reductive amination, as well as olefination and fluoroolefination with modified Julia and a Horner-Wadsworth-Emmons reagents.

General Approach to N6,C5'-Difunctionalization of Adenosine.

Among the C6-halo purine ribonucleosides, the readily accessible 6-chloro derivative has been known to undergo slow SNAr reactions with amines, particularly aryl amines. In this work, we show that in 0.1 M AcOH in EtOH, aryl amines react quite efficiently at the C6-position of 2',3',5'-tri-O-(t-BuMe2Si)-protected 6-chloropurine riboside (6-ClP-riboside), with concomitant cleavage of the 5'-silyl group. These two-step processes proceeded in generally good yields, and notably, reactions in the absence of AcOH were much slower and/or lower yielding. Corresponding reactions of 2',3',5'-tri-O-(t-BuMe2Si)-protected 6-ClP-riboside with alkyl amines proceeded well but without desilylation at the primary hydroxyl terminus. These differences are likely due to the acidities of the ammonium chlorides formed in these reactions, and the role of AcOH was not desilylation but possibly only purine activation. With 50% aqueous TFA in THF at 0 °C, cleavage of the 5'-silyl group from 2',3',5'-tri-O-(t-BuMe2Si)-protected N6-alkyl adenosine derivatives and from 6-ClP-riboside was readily achieved. Reactions of the 5'-deprotected 6-ClP-riboside with alkyl amines proceeded in high yields and under mild conditions. Because these complementary methodologies yielded N6-aryl and -alkyl adenosine derivatives containing a free 5'-hydroxyl group, a variety of product functionalizations were undertaken to yield N6,C5'-doubly modified nucleoside analogues.

Nuclear translocation of OsMFT1 that is impeded by OsFTIP1 promotes drought tolerance in rice.

Drought is the leading environmental threat affecting crop productivity, and plants have evolved a series of mechanisms to adapt to drought stress. The FT-interacting proteins (FTIPs) and phosphatidylethanolamine-binding proteins (PEBPs) play key roles in developmental processes, whereas their roles in the regulation of stress response are still largely unknown. Here, we report that OsFTIP1 negatively regulates drought response in rice. We showed that OsFTIP1 interacts with rice MOTHER OF FT AND TFL1 (OsMFT1), a PEBP that promotes rice tolerance to drought treatment. Further studies discovered that OsMFT1 interacts with two key drought-related transcription factors, OsbZIP66 and OsMYB26, regulating their binding capacity on drought-related genes and thereby enhancing drought tolerance in rice. Interestingly, we found that OsFTIP1 impedes the nucleocytoplasmic translocation of OsMFT1, implying that dynamic modulation of drought-responsive genes by the OsMFT1-OsMYB26 and OsMFT1-OsbZIP66 complexes is integral to OsFTIP1-modulated nuclear accumulation of OsMFT1. Our findings also suggest that OsMFT1 might act as a hitherto unknown nucleocytoplasmic trafficking signal that regulates drought tolerance in rice in response to environmental signals.

The prosthetic screw loosening of two-implant supported screw-retained fixed dental prostheses in the posterior region: A retrospective evaluation and finite element analysis.

The study was aimed to investigate the prosthetic screw loosening of two splinted implants-supported, screw-retained (2-4-unit) fixed dental prostheses (TIS-FDPs) in posterior region and to explore the underlying mechanism. In the retrospective study, a study group of TIS-FDPs (n = 23) presenting prosthetic screw loosening and a control group of TIS-FDPs (n = 32) absent of prosthetic screw loosening during observation period were included. The prosthesis height (PH), inter-implant distance (ID) and cantilever distance (CD) of TIS-FDPs were measured and compared within two groups. In the finite element analysis (FEA) part, three serials of models presenting different clinical scenarios were constructed based on the abovementioned PH, ID and CD values respectively. In the clinical evaluation, the values of pH and CD in study group were statistically higher than those in control group, whereas the values of ID had no significant difference. In the FEA, the results indicated that there was no linear correlation between the increased ID values and the maximum von Mises stresses and the rotation angles. On the other hand, the increased PH and CD values would result in a strong linear growth of the maximum von Mises stresses and the rotation angles. Besides, it was found that the regression coefficients in PH model were all higher than those in ID and CD models. When TIS-FDPs were delivered in posterior region, the PH and the CD, rather than the ID, seemed to have a significant impact on the stress concentration of the prosthetic screws and the incident of prosthetic screws loosening.

Assessing the Quality of Reporting to China's National TB Surveillance Systems.

(1) Background: The reliability of disease surveillance may be restricted by sensitivity or ability to capture all disease. Objective: To quantify under-reporting and concordance of recording persons with tuberculosis (TB) in national TB surveillance systems: the Infectious Disease Reporting System (IDRS) and Tuberculosis Information Management System (TBIMS). (2) Methods: This retrospective review includes 4698 patients identified in 2016 in China. County staff linked TB patients identified from facility-specific health and laboratory information systems with records in IDRS and TBIMS. Under-reporting was calculated, and timeliness, concordance, accuracy, and completeness were analyzed. Multivariable logistic regression was used to examine factors associated with under-reporting. (3) Results: We found that 505 (10.7%) patients were missing within IDRS and 1451 (30.9%) patients were missing within TBIMS. Of 171 patient records reviewed in IDRS and 170 patient records in TBIMS, 12.3% and 6.5% were found to be untimely, and 10.7% and 7.1% were found to have an inconsistent home address. The risk of under-reporting to both IDRS and TBIMS was greatest at tertiary health facilities and among non-residents; the risk of under-reporting to TBIMS was greatest with patients aged 65 or older and with extrapulmonary TB (EPTB). (4) Conclusions: It is important to improve the reporting and recording of TB patients. Local TB programs that focus on training, and mentoring high-burden hospitals, facilities that cater to EPTB, and migrant patients may improve reporting and recording.

Basal Takotsubo syndrome induced by pheochromocytoma rupture.

Takotsubo syndrome (TTS), characterised by transient left ventricular systolic dysfunction, is divided into five types: (1) apical ballooning, (2) mid-ventricular, (3) basal or inverted, (4) and focal wall-motion patterns, and (5) other types, including biventricular type, isolated right ventricular and global type. The common clinical features of TTS are similar to acute coronary syndrome, which makes them indistinguishable in the early stages. TTS has a wide spectrum of emotional or physical triggers. Pheochromocytoma has been widely recognised as a distinct physical trigger of TTS. Although reports of pheochromocytoma causing TTS are not uncommon, spontaneous rupture of pheochromocytoma causing TTS is extremely rare because of the low incidence of tumour rupture. Here we report on a case of a 31-year-old man with adrenal pheochromocytoma rupture developing basal TTS.

OsFTIP7 determines metallic oxide nanoparticles response and tolerance by regulating auxin biosynthesis in rice.

The widely application of metallic oxide nanoparticles (NPs) has led to an increase in their accumulation in farmland. Previous studies have found that the metallic oxide NPs have negative effect on plants development and growth. Nonetheless, the underlying mechanism of response to metallic oxide NPs in rice remains elusive. In this study, we show that rice FT-INTERACTING PROTEIN 7 (OsFTIP7) plays an essential role in NPs of CuO and ZnO-mediated physiological and biochemical changes in rice. Loss of function of OsFTIP7 reduced the toxicity of the NPs of CuO and ZnO to the seedlings by accumulating more biomass and chlorophyll contents. Furthermore, after high exposure to metallic oxide NPs, more indole-3-acetic acid (IAA) were determined in Osftip7 with higher expression of auxin biosynthetic genes than the control seedlings. What's more, IAA-treated seedlings displayed the similar phenotype as Osftip7 under high concentrations of NPs of CuO and ZnO. Taken together, the results substantiate that OsFTIP7 is involved in metallic oxide nanoparticle-mediated physiological and biochemical changes by negatively regulating auxin biosynthesis in rice.

Basal Takotsubo syndrome induced by pheochromocytoma rupture.

Takotsubo syndrome (TTS), characterised by transient left ventricular systolic dysfunction, is divided into five types: (1) apical ballooning, (2) mid-ventricular, (3) basal or inverted, (4) and focal wall-motion patterns, and (5) other types, including biventricular type, isolated right ventricular and global type. The common clinical features of TTS are similar to acute coronary syndrome, which makes them indistinguishable in the early stages. TTS has a wide spectrum of emotional or physical triggers. Pheochromocytoma has been widely recognised as a distinct physical trigger of TTS. Although reports of pheochromocytoma causing TTS are not uncommon, spontaneous rupture of pheochromocytoma causing TTS is extremely rare because of the low incidence of tumour rupture. Here we report on a case of a 31-year-old man with adrenal pheochromocytoma rupture developing basal TTS.

The Improvement of CRISPR-Cas9 System With Ubiquitin-Associated Domain Fusion for Efficient Plant Genome Editing.

Genome editing technology represented by CRISPR-Cas9 had been widely used in many biological fields such as gene function analysis, gene therapy, and crop improvement. However, in the face of the complexity of the eukaryotic genome, the CRISPR-Cas9 genome editing tools have shown an unstable editing efficiency with large variability at different target sites. It was important to further improve the editing efficiency of the CRISPR-Cas9 system among the whole genome. In this study, based on the previous single transcription unit genome editing system (STU-SpCas9), using the ubiquitin-associated domain (UBA) to enhance the stability of Cas9 protein, we constructed three Cas9-UBA fusion systems (SpCas9-SD01, SpCas9-SD02, and SpCas9-SD03). Four different target sites of rice OsPDS, OsDEP1 and OsROC5 genes were chosen to evaluate the genome editing efficiency in rice protoplasts and stable transformed rice plants. The results showed that the fusion of UBA domains did not affect the cleavage mode of Cas9 protein, and effectively increase the editing efficiency of STU-SpCas9 at the target sites. This new CRISPR-Cas9-UBA system provided a new strategy and tool for improving the genome editing efficiency of CRISPR-Cas9 in plants.