HERD-1 mediates multiphase condensate immiscibility to regulate small RNA-driven transgenerational epigenetic inheritance.

Biomolecular condensates, such as the nucleolus, stress granules/processing bodies and germ granules, are multiphase assemblages whose formation mechanisms and significance remain poorly understood. Here we identify protein constituents of the spatiotemporally ordered P, Z and M multiphase condensates in Caenorhabditis elegans germ granules using optimized TurboID-mediated proximity biotin labelling. These include 462, 41 and 86 proteins localizing to P, Z and M condensates, respectively, of which 522 were previously unknown protein constituents. Each condensate's proteins are enriched for distinct classes of structured and intrinsically disordered domains, suggesting divergent functions and assembly mechanisms. Through a functional screen, we identify a germ granule protein, HERD-1, which prevents the mixing of P, Z and M condensates. Mixing in herd-1 mutants correlates with disorganization of germline small RNA pathways and prolonged epigenetic inheritance of RNA interference-induced gene silencing. Forced mixing of these condensate components using a nanobody with specific binding activity against green fluorescent protein also extends epigenetic inheritance. We propose that active maintenance of germ granule immiscibility helps to organize and regulate small RNA-driven transgenerational epigenetic inheritance in C. elegans.

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy, as well as the current status of nanomedicine formulations of CBD, and discusses the potential and challenges of CBD in glioma therapy in the future.

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: the Guangzhou computerized tomography study.

Background: Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. Methods: All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Results: Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. Conclusions: A combination of PN and PC features allows statistical separation of DS and MDR cases.

Chinese expert consensus on imaging diagnosis of drug-resistant pulmonary tuberculosis.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB.

The sensitivity and specificity of 18F-FDG PET/CT in spinal leptomeningeal metastases: the synergistic effect of the 18F-FDG PET-CT to gadolinium-enhanced MRI.

Background: Magnetic resonance imaging (MRI) plays an important role in the diagnosis of leptomeningeal metastases (LM); however, some sub-centimeter lesions may be missed. Positron emission tomography/computed tomography (PET/CT) has a high sensitivity and may play a synergistic role with MRI in diagnosing spinal LM (SLM). We aimed to retrospectively evaluate the detection of SLM with 18F-fluorodeoxyglucose PET/CT (18F-FDG PET/CT) compared to that of whole spinal cord MRI in a single center. Methods: Patients with SLM who had undergone 18F-FDG PET/CT and MRI were enrolled. 18F-FDG PET/CT imaging findings were independently reviewed by 2 nuclear medicine physicians. 18F-FDG PET/CT findings of SLMs were described. A consistency test was conducted to assess the patient-based diagnostic results obtained by the 2 physicians. Patient-based sensitivity, accuracy, and specificity in diagnosing SLM between 18F-FDG PET/CT and MRI of the whole spinal cord were compared using the chi-square or Fisher's exact test. A P value of <0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was obtained to assess the diagnostic performance of maximum standardized uptake value (SUVmax) to diagnose SLM. Results: A total of 16 patients with SLM were included in this study from October 2010 to April 2022. The primary tumor involved the lungs, liver, ovaries, prostate, esophagus, and unknown primary site. The mean age of patients, including 13 males and 3 females, was 57.8±11.2 (range, 34-73) years. Of 16 patients with SLM, 10 had nodular diseases, 2 had linear diseases, and 4 had mixed diseases. The kappa value of the consistency test of the 2 radiologists' diagnostic results was 0.765. The patient-based sensitivity, specificity, and accuracy of 18F-FDG PET/CT in diagnosing SLM were 87.5%, 89.2%, and 88.7%, respectively and those of whole spinal cord MRI were 75.0%, 100.0%, and 92.5%, respectively. There were no significant differences in sensitivity, specificity, and accuracy between the 2 methods, with P values of 0.654, 0.115, and 0.506, respectively. However, more nodular diseases were observed on PET/CT. The area under the ROC curve (AUC) for the prediction of SLM by SUVmax was 0.907 [95% confidence interval (CI): 0.831-0.983]. When SUVmax ≥2.45, the Youden index was the largest, and the sensitivity and specificity were 89.3% and 75.7%, respectively. Conclusions: 18F-FDG PET/CT is a good choice of imaging modality for assessing SLM. In the diagnosis of SLMs, PET/CT and enhanced MRI can play a better synergistic role.

Gerhardtite as a Precursor to an Efficient CO-to-Acetate Electroreduction Catalyst.

Carbon-carbon coupling electrochemistry on a conventional copper (Cu) catalyst still undergoes low selectivity among many different multicarbon (C2+) chemicals, posing a grand challenge to achieve a single C2+ product. Here, we demonstrate a laser irradiation synthesis of a gerhardtite mineral, Cu2(OH)3NO3, as a catalyst precursor to make a Cu catalyst with abundant stacking faults under reducing conditions. Such structural perturbation modulates electronic microenvironments of Cu, leading to improved d-electron back-donation to the antibonding orbital of *CO intermediates and thus strengthening *CO adsorption. With increased *CO coverage on the defect-rich Cu, we report an acetate selectivity of 56 ± 2% (compared to 31 ± 1% for conventional Cu) and a partial current density of 222 ± 7 mA per square centimeter in CO electroreduction. When run at 400 mA per square centimeter for 40 h in a flow reactor, this catalyst produces 68.3 mmol of acetate throughout. This work highlights the value of a Cu-containing mineral phase in accessing suitable structures for improved selectivity to a single desired C2+ product.

Machine learning-based models for predicting gas breakthrough pressure of porous media with low/ultra-low permeability.

Gas breakthrough pressure is a significant parameter for the gas exploration and safety evaluation of engineering barrier systems in the carbon dioxide storage, remediation of contaminated sites, and deep geological repository for disposal of high-level nuclear waste, etc. Test for determining gas breakthrough pressure is very difficult and time-consuming, due to the low/ultra-low conductivity of the specimen. It is also difficult to get a comprehensive and high-precision model based on limited results obtained through individual experiments, as the measurements of gas breakthrough pressure were influenced by many factors. In this study, a collected database was built that covered a lot of former test data, and then, two models were developed by the random forest (RF) algorithm and multiexpression programming (MEP) method. The MEP model constructed with explicit expressions for the gas breakthrough pressure overcame the drawbacks of common "black box" models. Meanwhile, five significant indicators were selected from ten common features using the permutation importance algorithm. The RF model was interpreted by the Shapley value and the PDP/ICE plots, while the MEP model was analyzed through the proposed explicit expression, showing strong consistence with that in former studies. Finally, robustness analysis was conducted, and stability of the proposed two models was verified.

Annotations of Lung Abnormalities in Shenzhen Chest X-ray Dataset for Computer-Aided Screening of Pulmonary Diseases.

Developments in deep learning techniques have led to significant advances in automated abnormality detection in radiological images and paved the way for their potential use in computer-aided diagnosis (CAD) systems. However, the development of CAD systems for pulmonary tuberculosis (TB) diagnosis is hampered by the lack of training data that is of good visual and diagnostic quality, of sufficient size, variety, and, where relevant, containing fine region annotations. This study presents a collection of annotations/segmentations of pulmonary radiological manifestations that are consistent with TB in the publicly available and widely used Shenzhen chest X-ray (CXR) dataset made available by the U.S. National Library of Medicine and obtained via a research collaboration with No. 3. People's Hospital Shenzhen, China. The goal of releasing these annotations is to advance the state-of-the-art for image segmentation methods toward improving the performance of fine-grained segmentation of TB-consistent findings in digital Chest X-ray images. The annotation collection comprises the following: 1) annotation files in JSON (JavaScript Object Notation) format that indicate locations and shapes of 19 lung pattern abnormalities for 336 TB patients; 2) mask files saved in PNG format for each abnormality per TB patient; 3) a CSV (comma-separated values) file that summarizes lung abnormality types and numbers per TB patient. To the best of our knowledge, this is the first collection of pixel-level annotations of TB-consistent findings in CXRs. Dataset: https://data.lhncbc.nlm.nih.gov/public/Tuberculosis-Chest-X-ray-Datasets/Shenzhen-Hospital-CXR-Set/Annotations/index.html.

Boundary TextSpotter: Toward Arbitrary-Shaped Scene Text Spotting.

Reading arbitrary-shaped text in an end-to-end fashion has received particularly growing interested in computer vision. In this paper, we study the problem of scene text spotting, which aims to detect and recognize text from cluttered images simultaneously and propose an end-to-end trainable neural network named Boundary TextSpotter. Different from existing methods that describe the shape of text instance with bounding box or shape mask, Boundary TextSpotter formulates it as a set of boundary points. Besides, the representation of such boundary points provides the order of reading text. Benefiting from the representation on both detection and recognition, Boundary TextSpotter can easily deal with the text of arbitrary shapes. Further, to efficiently detect the boundary points of the text, a single-stage text detector is proposed, which can almost perform at a real-time speed. Experiments on three challenging datasets, including ICDAR2015, Total-Text and CTW1500 demonstrate that the proposed method achieves state-of-the-art or competitive results, meanwhile significantly improving the inference speed.

Role of 18F-FDG PET/CT in the diagnosis and management of patients with Langerhans cell histiocytosis.

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that can involve multisystem organs. Positron emission tomography/computed tomography (PET/CT) has been widely used in tumor staging and efficacy evaluation. However, at present, there are few 18F-fluorodeoxyglucose (FDG) PET/CT studies on LCH. This study aimed to explore the possible role of 18F-FDG PET/CT in the diagnosis and management of patients with LCH. Methods: 18F-FDG PET/CT images of 22 Chinese patients diagnosed with LCH on biopsy or surgery histopathology between January 2011 and December 2020 were retrospectively analyzed. The incidence of LCH in each system was assessed by a PET/CT scan. The imaging characteristics were analyzed semiquantitatively and qualitatively. The discrepancies between PET/CT and conventional imaging modalities were recorded. Evaluations of curative effect according to RECIST1.1 and PERCIST1.0 were compared using Fisher's exact chi-squared test, and P values <0.05 were considered significant. Results: Eight (36.4%) of the 22 patients presented with single system involvement (4 isolated site involvement, 4 multiple site involvement), and 14 (63.6%) presented with multiple system involvement. Twenty-one (95.5%) patients had hypermetabolic lesions. Musculoskeletal, lymphatic, respiratory, liver, skin-soft tissue and thyroid involvement were seen in 14 (63.6%), 13 (59.1%), 5 (22.7%), 4 (18.2%), 5 (22.7%) and 1 (4.5%) patient, respectively. Cranial and facial bones were the most common sites of musculoskeletal involvement. Ten patients underwent PET/CT follow-up, and there was no significant difference in curative effect evaluations according to RECIST1.1 and PERCIST1.0. However, among the complete remission cases assessed by RECIST1.1, three were partial metabolic responses assessed by PERCIST1.0, while among the partial response cases assessed by RECIST1.1, one was metabolic progressive disease assessed by PERCIST1.0. Conclusions: 18F-FDG PET/CT is an imaging modality option for the diagnosis and assessment of the curative effect of LCH.

Recognition of Upper Limb Action Intention Based on IMU.

Using motion information of the upper limb to control the prosthetic hand has become a hotspot of current research. The operation of the prosthetic hand must also be coordinated with the user's intention. Therefore, identifying action intention of the upper limb based on motion information of the upper limb is key to controlling the prosthetic hand. Since a wearable inertial sensor bears the advantages of small size, low cost, and little external environment interference, we employ an inertial sensor to collect angle and angular velocity data during movement of the upper limb. Aiming at the action classification for putting on socks, putting on shoes and tying shoelaces, this paper proposes a recognition model based on the Dynamic Time Warping (DTW) algorithm of the motion unit. Based on whether the upper limb is moving, the complete motion data are divided into several motion units. Considering the delay associated with controlling the prosthetic hand, this paper only performs feature extraction on the first motion unit and the second motion unit, and recognizes action on different classifiers. The experimental results reveal that the DTW algorithm based on motion unit bears a higher recognition rate and lower running time. The recognition rate reaches as high as 99.46%, and the average running time measures 8.027 ms. In order to enable the prosthetic hand to understand the grasping intention of the upper limb, this paper proposes a Generalized Regression Neural Network (GRNN) model based on 10-fold cross-validation. The motion state of the upper limb is subdivided, and the static state is used as the sign of controlling the prosthetic hand. This paper applies a 10-fold cross-validation method to train the neural network model to find the optimal smoothing parameter. In addition, the recognition performance of different neural networks is compared. The experimental results show that the GRNN model based on 10-fold cross-validation exhibits a high accuracy rate, capable of reaching 98.28%. Finally, the two algorithms proposed in this paper are implemented in an experiment of using the prosthetic hand to reproduce an action, and the feasibility and practicability of the algorithm are verified by experiment.

Discovery of Reldesemtiv, a Fast Skeletal Muscle Troponin Activator for the Treatment of Impaired Muscle Function.

The discovery of reldesemtiv, a second-generation fast skeletal muscle troponin activator (FSTA) that increases force production at submaximal stimulation frequencies, is reported. Property-based optimization of high throughput screening hit 1 led to compounds with improved free exposure and in vivo muscle activation potency compared to the first-generation FSTA, tirasemtiv. Reldesemtiv demonstrated increased muscle force generation in a phase 1 clinical trial and is currently being evaluated in clinical trials for the treatment of amyotrophic lateral sclerosis.

Knockdown of ghAlba_4 and ghAlba_5 Proteins in Cotton Inhibits Root Growth and Increases Sensitivity to Drought and Salt Stresses.

We found 33, 17, and 20 Alba genes in Gossypium hirsutum, Gossypium arboretum, and Gossypium raimondii, respectively. The Alba protein lengths ranged from 62 to 312 aa, the molecular weight (MW) from 7.003 to 34.55 kDa, grand average hydropathy values of -1.012 to 0.609 and isoelectric (pI) values of -3 to 11. Moreover, miRNAs such as gra-miR8770 targeted four genes, gra-miR8752 and gra-miR8666 targeted three genes, and each and gra-miR8657 a, b, c, d, e targeted 10 genes each, while the rests targeted 1 to 2 genes each. Similarly, various cis-regulatory elements were detected with significant roles in enhancing abiotic stress tolerance, such as CBFHV (RYCGAC) with a role in cold stress acclimation among others. Two genes, Gh_D01G0884 and Gh_D01G0922, were found to be highly induced under water deficit and salt stress conditions. Through virus-induced gene silencing (VIGS), the VIGS cotton plants were found to be highly susceptible to both water deficit and salt stresses; the VIGS plants exhibited a significant reduction in root growth, low cell membrane stability (CMS), saturated leaf weight (SLW), chlorophyll content levels, and higher excised leaf water loss (ELWL). Furthermore, the stress-responsive genes and ROS scavenging enzymes were significantly reduced in the VIGS plants compared to either the wild type (WT) and or the positively controlled plants. The VIGS plants registered higher concentration levels of hydrogen peroxide and malondialdehyde, with significantly lower levels of the various antioxidants evaluated an indication that the VIGS plants were highly affected by salt and drought stresses. This result provides a key foundation for future exploration of the Alba proteins in relation to abiotic stress.

Map-Based Functional Analysis of the GhNLP Genes Reveals Their Roles in Enhancing Tolerance to N-Deficiency in Cotton.

Nitrogen is a key macronutrient needed by plants to boost their production, but the development of cotton genotypes through conventional approaches has hit a bottleneck due to the narrow genetic base of the elite cotton cultivars, due to intensive selection and inbreeding. Based on our previous research, in which the BC2F2 generations developed from two upland cotton genotypes, an abiotic stress-tolerant genotype, G. tomentosum (donor parent) and a highly-susceptible, and a highly-susceptible, but very productive, G. hirsutum (recurrent parent), were profiled under drought stress conditions. The phenotypic and the genotypic data generated through genotyping by sequencing (GBS) were integrated to map drought-tolerant quantitative trait loci (QTLs). Within the stable QTLs region for the various drought tolerance traits, a nodule-inception-like protein (NLP) gene was identified. We performed a phylogenetic analysis of the NLP proteins, mapped their chromosomal positions, intron-exon structures and conducted ds/dn analysis, which showed that most NLP genes underwent negative or purifying selection. Moreover, the functions of one of the highly upregulated genes, Gh_A05G3286 (Gh NLP5), were evaluated using the virus gene silencing (VIGS) mechanism. A total of 226 proteins encoded by the NLP genes were identified, with 105, 61, and 60 in Gossypium hirsutum, G. raimondii, and G. arboreum, respectively. Comprehensive Insilico analysis revealed that the proteins encoded by the NLP genes had varying molecular weights, protein lengths, isoelectric points (pI), and grand hydropathy values (GRAVY). The GRAVY values ranged from a negative one to zero, showing that proteins were hydrophilic. Moreover, various cis-regulatory elements that are the binding sites for stress-associated transcription factors were found in the promoters of various NLP genes. In addition, many miRNAs were predicted to target NLP genes, notably miR167a, miR167b, miR160, and miR167 that were previously shown to target five NAC genes, including NAC1 and CUC1, under N-limited conditions. The real-time quantitative polymerase chain reaction (RT-qPCR) analysis, revealed that five genes, Gh_D02G2018, Gh_A12G0439, Gh_A03G0493, Gh_A03G1178, and Gh_A05G3286 were significantly upregulated and perhaps could be the key NLP genes regulating plant response under N-limited conditions. Furthermore, the knockdown of the Gh_A05G3286 (GhNLP5) gene by virus-induced silencing (VIGS) significantly reduced the ability of these plants to the knockdown of the Gh_A05G3286 (GhNLP5) gene by virus-induced gene silencing (VIGS) significantly reduced the ability of the VIGS-plants to tolerate N-limited conditions compared to the wild types (WT). The VIGS-plants registered lower chlorophyll content, fresh shoot biomass, and fresh root biomass, addition to higher levels of malondialdehyde (MDA) and significantly reduced levels of proline, and superoxide dismutase (SOD) compared to the WT under N-limited conditions. Subsequently, the expression levels of the Nitrogen-stress responsive genes, GhTap46, GhRPL18A, and GhKLU were shown to be significantly downregulated in VIGS-plants compared to their WT under N-limited conditions. The downregulation of the nitrogen-stress responsive genes provided evidence that the silenced gene had an integral role in enhancing cotton plant tolerance to N-limited conditions.

Genome-wide analysis of the cotton G-coupled receptor proteins (GPCR) and functional analysis of GTOM1, a novel cotton GPCR gene under drought and cold stress.

BACKGROUND: The efficient detection and initiation of appropriate response to abiotic stresses are important to plants survival. The plant G-protein coupled receptors (GPCRs) are diverse membranous proteins that are responsible for signal transduction. RESULTS: In this research work, we identified a novel gene of the GPCR domain, transformed and carried out the functional analysis in Arabidopsis under drought and cold stresses. The transgenic lines exposed to drought and cold stress conditions showed higher germination rate, increased root length and higher fresh biomass accumulation. Besides, the levels of antioxidant enzymes, glutathione (GSH) and ascorbate peroxidase (APX) exhibited continuously increasing trends, with approximately threefold higher than the control, implying that these ROS-scavenging enzymes were responsible for the detoxification of ROS induced by drought and cold stresses. Similarly, the transgenic lines exhibited stable cell membrane stability (CMS), reduced water loss rate in the detached leaves and significant values for the saturated leaves compared to the wild types. Highly stress-responsive miRNAs were found to be targeted by the novel gene and based on GO analysis; the protein encoded by the gene was responsible for maintaining an integral component of membrane. In cotton, the virus-induced gene silencing (VIGS) plants exhibited a higher susceptibility to drought and cold stresses compared to the wild types. CONCLUSION: The novel GPCR gene enhanced drought and cold stress tolerance in transgenic Arabidopsis plants by promoting root growth and induction of ROS scavenging enzymes. The outcome showed that the gene had a role in enhancing drought and cold stress tolerance, and can be further exploited in breeding for more stress-resilient and tolerant crops.

Updates on 18F-FDG-PET/CT as a clinical tool for tuberculosis evaluation and therapeutic monitoring.

Tuberculosis (TB) is currently the world's leading cause of infectious mortality. The complex immune response of the human body to Mycobacterium tuberculosis (M.tb) results in a wide array of clinical manifestations, thus the clinical and radiological diagnosis can be challenging. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scan with/without computed tomography (CT) component images the whole body and provides a metabolic map of the infection, enabling clinicians to assess the disease burden. 18F-FDG-PET/CT scan is particularly useful in detecting the disease in previously unknown sites, and allows the most appropriate site of biopsy to be selected. 18F-FDG-PET/CT is also very valuable in assessing early disease response to therapy, and plays an important role in cases where conventional microbiological methods are unavailable and for monitoring response to therapy in cases of multidrug-resistant TB or extrapulmonary TB. 18F-FDG-PET/CT cannot reliably differentiate active TB lesion from malignant lesions and false positives can also be due to other infective or inflammatory conditions. 18F-FDG PET is also unable to distinguish tuberculous lymphadenitis from metastatic lymph node involvement. The lack of specificity is a limitation for 18F-FDG-PET/CT in TB management.

Functional characterization of Gh_A08G1120 (GH3.5) gene reveal their significant role in enhancing drought and salt stress tolerance in cotton.

BACKGROUND: Auxins play an important role in plant growth and development; the auxins responsive gene; auxin/indole-3-acetic acid (Aux/IAA), small auxin-up RNAs (SAUR) and Gretchen Hagen3 (GH3) control their mechanisms. The GH3 genes function in homeostasis by the catalytic activities in auxin conjugation and bounding free indole-3-acetic acid (IAA) to amino acids. RESULTS: In our study, we identified the GH3 genes in three cotton species; Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii, analyzed their chromosomal distribution, phylogenetic relationships, cis-regulatory element function and performed virus induced gene silencing of the novel Gh_A08G1120 (GH3.5) gene. The phylogenetic tree showed four clusters of genes with clade 1, 3 and 4 having mainly members of the GH3 of the cotton species while clade 2 was mainly members belonging to Arabidopsis. There were no paralogous genes, and few orthologous genes were observed between Gossypium and other species. All the GO terms were detected, but only 14 genes were found to have described GO terms in upland cotton, more biological functions were detected, as compared to the other functions. The GH3.17 subfamily harbored the highest number of the cis-regulatory elements, most having promoters towards dehydration-responsiveness. The RNA expression analysis revealed that 10 and 8 genes in drought and salinity stress conditions respectively were upregulated in G. hirsutum. All the genes that were upregulated in plants under salt stress conditions were also upregulated in drought stress; moreover, Gh_A08G1120 (GH3.5) exhibited a significant upregulation across the two stress factors. Functional characterization of Gh_A08G1120 (GH3.5) through virus-induced gene silencing (VIGS) revealed that the VIGS plants ability to tolerate drought and salt stresses was significantly reduced compared to the wild types. The chlorophyll content, relative leaf water content (RLWC), and superoxide dismutase (SOD) concentration level were reduced significantly while malondialdehyde concentration and ion leakage as a measure of cell membrane stability (CMS) increased in VIGS plants under drought and salt stress conditions. CONCLUSION: This study revealed the significance of the GH3 genes in enabling the plant's adaptation to drought and salt stress conditions as evidenced by the VIGS results and RT-qPCR analysis.

Correlation between 18F-FDG PET CT SUV and symptomatic or asymptomatic pulmonary tuberculosis.

OBJECTIVE: To explore the difference of 18F-FDG PET/CT images between the symptomatic and asymptomatic pulmonary tuberculosis, as well as the correlation between the standard uptake value (SUV) and the symptomatic/asymptomatic pulmonary tuberculosis. METHODS: A study dataset of 57 pulmonary tuberculosis cases was retrospectively assembled and analyzed. Among these cases, 30 were diagnosed having symptomatic pulmonary tuberculosis and 27 were asymptomatic pulmonary tuberculosis. PET/CT was performed in all 57 cases. The clinical data, CT images and PET/CT radioactive uptake data were analyzed using statistical data analysis software. RESULTS: All 57 cases showed radioactively high uptake, with the maximum standard uptake value (SUVmax) of the lesion ranging from 1.60 to 27.30 and a mean value of 6.63±4.82. The symptomatic cases had an SUVmax of 8.76±4.97 and the asymptomatic cases had an SUVmax of 4.27±3.39. The SUVmax as well as singular or multiple lesions showed statistical differences between symptomatic and asymptomatic cases. CONCLUSION: The symptomatic pulmonary tuberculosis cases show significantly higher SUVmax than the asymptomatic cases. Based on the criteria of SUVmax greater than 2.0 to define active lesions, 100% of symptomatic cases might have active lesions while 70.4% of asymptomatic cases might have active lesions. Therefore, focused attention should be clinically paid on the asymptomatic cases of pulmonary tuberculosis to avoid miss diagnosis and delayed treatment.

Overexpression of Cotton a DTX/MATE Gene Enhances Drought, Salt, and Cold Stress Tolerance in Transgenic Arabidopsis.

Abiotic stresses have negative effects on plants growth and development. Plants, being sessile, have developed specific adaptive strategies that allow them to rapidly detect and respond to abiotic stress factors. The detoxification efflux carriers (DTX)/multidrug and toxic compound extrusion (MATE) transporters are of significance in the translocation of abscisic acid (ABA), a phytohormone with profound role in plants under various abiotic stress conditions. The ABA signaling cascades are the core regulators of abiotic stress responses in plants, triggering major changes in gene expression and adaptive physiological responses. We therefore carried out genome-wide analysis of the DTX/MATE gene family, transformed a DTX/MATE gene in Arabidopsis and carried out functional analysis under drought, salt, and cold stress conditions. We identified 128, 70, and 72 DTX/MATE genes in Gossypium hirsutum, Gossypium arboreum, and Gossypium raimondii, respectively. The proteins encoded by the DTX/MATE genes showed varied physiochemical properties but they all were hydrophobic. The Gh_D06G0281 (DTX/MATE) over-expressing Arabidopsis lines were highly tolerant under drought, salt, and cold stress with high production of antioxidant enzymes and significantly reduced levels of oxidants. Lipid peroxidation, as measured by the level of malondialdehyde concentrations was relatively low in transgenic lines compared to wild types, an indication of reduced oxidative stress levels in the transgenic plants. Based on physiological measurements, the transgenic plants exhibited significantly higher relative leaf water content, reduced excised leaf water loss and a significant reduction in ion leakage as a measure of the cell membrane stability compared to the wild types. Abiotic stress responsive genes, ABF4, CBL1, SOS1, and RD29B were highly expressed in the transgenic lines compared to the non-transformed wild type plants. The protein encoded by the Gh_D06G0281 (DTX/MATE) gene was predicted to be located within the plasma membrane. Since signals from extracellular stimuli are transmitted through the plasma membrane most of which are conducted by plasma membrane proteins it is possible the Gh_D06G0281 (DTX/MATE) gene product could be important for this process.

Knockdown of Cytochrome P450 Genes Gh_D07G1197 and Gh_A13G2057 on Chromosomes D07 and A13 Reveals Their Putative Role in Enhancing Drought and Salt Stress Tolerance in Gossypium hirsutum.

We identified 672, 374, and 379 CYPs proteins encoded by the CYPs genes in Gossypiumhirsutum, Gossypiumraimondii, and Gossypiumarboreum, respectively. The genes were found to be distributed in all 26 chromosomes of the tetraploid cotton, with chrA05, chrA12, and their homeolog chromosomes harboring the highest number of genes. The physiochemical properties of the proteins encoded by the CYP450 genes varied in terms of their protein lengths, molecular weight, isoelectric points (pI), and even grand hydropathy values (GRAVY). However, over 99% of the cotton proteins had GRAVY values below 0, which indicated that the majority of the proteins encoded by the CYP450 genes were hydrophilic in nature, a common property of proteins encoded by stress-responsive genes. Moreover, through the RNA interference (RNAi) technique, the expression levels of Gh_D07G1197 and Gh_A13G2057 were suppressed, and the silenced plants showed a higher concentration of hydrogen peroxide (H2O2) with a significant reduction in the concentration levels of glutathione (GSH), ascorbate peroxidase (APX), and proline compared to the wild types under drought and salt stress conditions. Furthermore, the stress-responsive genes 1-Pyrroline⁻5-Carboxylate Synthetase (GhP5CS), superoxide dismutase (GhSOD), and myeloblastosis (GhMYB) were downregulated in VIGS plants, but showed upregulation in the leaf tissues of the wild types under drought and salt stress conditions. In addition, CYP450-silenced cotton plants exhibited a high level of oxidative injury due to high levels of oxidant enzymes, in addition to negative effects on CMS, ELWL, RLWC, and chlorophyll content The results provide the basic foundation for future exploration of the proteins encoded by the CYP450 genes in order to understand the physiological and biochemical mechanisms in enhancing drought and salt stress tolerance in plants.