Positioning of pyrimidine motifs around cassette exons defines their PTB-dependent splicing in Arabidopsis.

Alternative splicing (AS) is a complex process that generates transcript variants from a single pre-mRNA and is involved in numerous biological functions. Many RNA-binding proteins are known to regulate AS; however, little is known about the underlying mechanisms, especially outside the mammalian clade. Here, we show that polypyrimidine tract binding proteins (PTBs) from Arabidopsis thaliana regulate AS of cassette exons via pyrimidine (Py)-rich motifs close to the alternative splice sites. Mutational studies on three PTB-dependent cassette exon events revealed that only some of the Py motifs in this region are critical for AS. Moreover, in vitro binding of PTBs did not reflect a motif's impact on AS in vivo. Our mutational studies and bioinformatic investigation of all known PTB-regulated cassette exons from A. thaliana and human suggested that the binding position of PTBs relative to a cassette exon defines whether its inclusion or skipping is induced. Accordingly, exon skipping is associated with a higher frequency of Py stretches within the cassette exon, and in human also upstream of it, whereas exon inclusion is characterized by increased Py motif occurrence downstream of said exon. Enrichment of Py motifs downstream of PTB-activated 5' splice sites is also seen for PTB-dependent intron removal and alternative 5' splice site events from A. thaliana, suggesting this is a common step of exon definition. In conclusion, the position-dependent AS regulatory mechanism by PTB homologs has been conserved during the separate evolution of plants and mammals, while other critical features, in particular intron length, have considerably changed.

A transient in planta editing assay identifies specific binding of the splicing regulator PTB as a prerequisite for cassette exon inclusion.

The dynamic interaction of RNA-binding proteins (RBPs) with their target RNAs contributes to the diversity of ribonucleoprotein (RNP) complexes that are involved in a myriad of biological processes. Identifying the RNP components at high resolution and defining their interactions are key to understanding their regulation and function. Expressing fusions between an RBP of interest and an RNA editing enzyme can result in nucleobase changes in target RNAs, representing a recent addition to experimental approaches for profiling RBP/RNA interactions. Here, we have used the MS2 protein/RNA interaction to test four RNA editing proteins for their suitability to detect target RNAs of RBPs in planta. We have established a transient test system for fast and simple quantification of editing events and identified the hyperactive version of the catalytic domain of an adenosine deaminase (hADARcd) as the most suitable editing enzyme. Examining fusions between homologs of polypyrimidine tract binding proteins (PTBs) from Arabidopsis thaliana and hADARcd allowed determining target RNAs with high sensitivity and specificity. Moreover, almost complete editing of a splicing intermediate provided insight into the order of splicing reactions and PTB dependency of this particular splicing event. Addition of sequences for nuclear localisation of the fusion protein increased the editing efficiency, highlighting this approach's potential to identify RBP targets in a compartment-specific manner. Our studies have established the editing-based analysis of interactions between RBPs and their RNA targets in a fast and straightforward assay, offering a new system to study the intricate composition and functions of plant RNPs in vivo.

Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB).

BACKGROUND: Prenatal exposure to intrauterine inflammation (IUI) is a crucial event in preterm birth (PTB) pathophysiology, increasing the incidence of neurodevelopmental disorders. Gut microbiota and metabolite profile alterations have been reported to be involved in PTB pathophysiology. METHOD AND RESULTS: In this study, IUI-exposed PTB mouse model was established and verified by PTB rate and other perinatal adverse reactions; LPS-indued IUI significantly increased the rates of PTB, apoptosis and inflammation in placenta tissue samples. LPS-induced IUI caused no significant differences in species richness and evenness but significantly altered the species abundance distribution. Non-targeted metabolomics analysis indicated that the metabolite profile of the preterm mice was altered, and differential metabolites were associated with signaling pathways including pyruvate metabolism. Furthermore, a significant positive correlation between Parasutterella excrementihominis and S4572761 (Nb-p-coumaroyltryptamine) and Mreference-1264 (pyruvic acid), respectively, was observed. Lastly, pyruvic acid treatment partially improved LPS-induced IUI phenotypes and decreased PTB rates and decreased the apoptosis and inflammation in placenta tissue samples. CONCLUSION: This study revealed an association among gut microbiota dysbiosis, metabolite profile alterations, and LPS-induced IUI and PTB in mice models. Our investigation revealed the possible involvement of gut microbiota in the pathophysiology of LPS-induced IUI and PTB, which might be mediated by metabolites such as pyruvic acid. Future studies should be conducted to verify the findings through larger sample-sized animal studies and clinical investigations.

Preterm birth in singleton pregnancies conceived by in vitro fertilization or intracytoplasmic sperm injection: an overview of systematic reviews.

BACKGROUND: The rate of preterm birth of singletons conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is increased, being as high as 15% to 16% across Europe and the United States. However, the underlying etiology, phenotype, and mechanisms initiating preterm birth (PTB) are poorly understood. OBJECTIVE: To quantify the PTB risk and examine supposed etiology in IVF/ICSI singleton pregnancies compared to naturally conceived. STUDY DESIGN: Overview of reviews including all available systematic reviews with meta-analysis comparing PTB risk in IVF/ICSI and naturally conceived singletons. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was performed up to December 31, 2023. Information available on etiology, phenotype, initiation of PTB, and relevant moderators was retrieved and employed for subgroup analyses. Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The extent of overlap in the original studies was measured using the corrected covered area assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to rate evidence certainty. The protocol was registered on PROspective Register of Systematic Reviews (CRD42023411418). RESULTS: Twelve meta-analyses (16,522,917 pregnancies; ˃433,330 IVF/ICSI) were included. IVF/ICSI singletons showed a significantly higher PTB risk compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89; PTB<32 weeks: OR: 2.19, 95% CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR: 1.79, 95% CI: 1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95% CI: 1.72-3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh only (OR: 1.79, 95% CI: 1.55-2.07) vs frozen-thawed embryo transfers (OR: 1.39, 95% CI: 1.34-1.43). There was minimal study overlap (13%). The certainty of the evidence was graded as low to very low. CONCLUSION: Singletons conceived through IVF/ICSI have a 2-fold increased risk of PTB compared to natural conception, despite the low certainty of the evidence. There is paucity of available data on PTB etiology, phenotype, or initiation. The greater risk increase is observed in fresh embryo transfers and involves iatrogenic PTB and PTB ˂32 weeks, likely attributable to placental etiology. Future studies should collect data on PTB etiology, phenotype, and initiation. IVF/ICSI pregnancies should undertake specialistic care with early screening for placental disorders, cervical length, and growth abnormalities, allowing appropriate timely follow-up, preventive measures, and therapeutic interventions strategies.

Bacilli load in PTB- intestinal helminths co-infected and PTB non -infected patients at selected public health facilities in Jimma zone, Oromia, Ethiopia: comparative cross-sectional study.

BACKGROUND: Tuberculosis (TB) and intestinal helminths are diseases that pose a dual burden on public health in low-income countries. Previous studies have shown that helminths can affect the shedding of bacteria or the bacterial load in the sputum of active TB patients. However, there is limited information on bacterial load in TB patients with helminth infections. OBJECTIVE: This study aimed to compare bacterial load in helminths-infected and non-infected pulmonary tuberculosis patients at selected public health facilities in Jimma zone, Oromia, Ethiopia. METHODS: The study was conducted in Jimma Zone, Oromia, Ethiopia. A facility-based comparative cross-sectional study was employed from August 01, 2020, to January 2021. A total of 124 (55 intestinal helminths-infected and 69 non-infected) newly diagnosed smear-positive pulmonary tuberculosis (PTB) patients were included in the study. A convenience sampling technique was employed to recruit study participants, and a semi-structured questionnaire was used to collect data regarding socio-demographic characteristics and possible risk factors for intestinal helminths co-infection. Stool examination was performed using both wet mount and Kato Katz technique. Additionally, weight and height measurements, sputum, and blood samples were taken to determine body mass index, bacilli load, and diabetic mellitus, respectively. Data were entered into Epi-Data software version 3.1 and analyzed using Statistical Packages for Social Sciences (SPSS) Version 25. A statistically significant difference was defined as a P-value of less than 0.05. RESULTS: Intestinal helminths reduced bacilli load 3 times more than intestinal helminths non-infected PTB (AOR = 3.44; 95% CI; 1.52, 7.79; P = 0.003) However, diabetes mellitus, HIV, drinking alcohol and cigarette smoking were not associated with bacilli load. The rate of co-infection TB with intestinal helminths was 44%. The three most prevalent parasites detected were Trichuris trichiura 29 (66%), hookworm 19 (43%), and Ascaris lumbricoides 11(25%)). Among co-infected patients about 36 (81.8%) had a single parasite infection, and 19 (43.2%) had multiple infections. A body mass index < 18.5 (AOR = 3.26; 95% CI; 1.25, 8.56;P = 0.016) and untrimmed fingernail status (AOR = 3.63; 95%CI;1.32,9.93;P = 0.012) were significantly associated with PTB- intestinal helminth -co-infection. CONCLUSION: Helminth infection was associated with a lower bacilli load compared to helmenths non-infected PTB. The rate of co-infection TB with intestinal helminths was 44%. Trichuris trichiura was the most prevalent helminth. Untrimmed fingernail and a body mass index were associated with PTB-intestinal helminth co-infection.

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient.

BACKGROUND: Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. CASE PRESENTATION: The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. CONCLUSION: Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

CXCL9/CXCL10 as biomarkers the monitoring of treatment responses in Pulmonary TB patients: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a persistent threat to global public health and traditional treatment monitoring approaches are limited by their potential for contamination and need for timely evaluation. Therefore, new biomarkers are urgently required for monitoring the treatment efficacy of TB. METHODS: This study aimed to elucidate the levels of CXCL10 and CXCL9 in pulmonary TB patients who underwent anti-TB treatment. The data was acquired from five databases, including PubMed, Ovid, Web of Science, Embase, and the Cochrane Library. A meta-analysis of CXCL10 data from all time points was conducted. Furthermore, a trend meta-analysis of temporal data of CXCL10 and CXCL9 from multiple time points was also performed. RESULTS: It was revealed that patients who responded poorly to anti-TB treatment had higher serum levels relative to those who responded well (SMD: 1.23, 95% CI: -0.37-2.84) at the end of intensive treatment (2 months). Furthermore, heterogeneity was observed in these results, which might be because patients with a prior history of TB and different treatment monitoring methods than those selected in this study were also included. The analysis of alterations in CXCL10 and CXCL9 levels since the last collection time points indicated that their levels reduced with time. CONCLUSION: In summary, the study revealed that reductions in CXCL10 levels during the first two months of anti-TB treatment are correlated with treatment responses. Furthermore, decreasing levels of CXCL9 during the treatment suggest that it may also serve as a biomarker with a similar value to CXCL10. Future in-depth studies are thus warranted to further probe the relevance of CXCL10 and CXCL9 in monitoring the treatment efficacy of TB.

Decreased mRNA expression of NR1H3 and ABCA1 in pulmonary tuberculosis patients from population of Punjab, India.

BACKGROUND: Mycobacterium tuberculosis (MTB) is the causative organism of tuberculosis. Cholesterol is a crucial carbon source required for the survival of MTB in host cells. Transcription factor NR1H3 along with its important target genes ABCA1 and ApoE play important role in removal of extra cholesterol from cells. Changes in the gene expression of NR1H3, ABCA1 and ApoE can affect cholesterol homeostasis and thus the survival of MTB in host cells.Therefore, the present study was designed to analyze the mRNA expression of NR1H3, ABCA1 and ApoE in pulmonary TB (PTB) patients from the population of Punjab, India. METHODS AND RESULTS: In this study, mRNA expression of the transcription factor NR1H3 and its target genes ABCA1 and ApoE was analyzed in 89 subjects, including 41 PTB patients and 48 healthy controls (HCs) by real-time quantitative PCR. It was found that the mRNA expression of both NR1H3 and ABCA1 genes was significantly lower in TB patients than in HCs (p < 0.001). Even after sex-wise stratification of the subjects, mRNA expression of NR1H3 and ABCA1 was found to be down-regulated in both male and female TB patients. No significant difference was observed in expression of ApoE (p = 0.98). CONCLUSIONS: The present study found that the mRNA expression of NR1H3 and ABCA1 is down-regulated in TB patients from Punjab state of India.

Optimized anti-tuberculosis duration for drug-susceptible pulmonary tuberculosis-diabetes mellitus comorbidities: study protocol for a multicenter randomized controlled trial.

BACKGROUND: The coexistence of tuberculosis (TB) and type 2 diabetes mellitus (DM) presents unique challenges in treatment optimization and management, given the mutual exacerbation of disease processes. OBJECTIVE: This multicenter, open-label, randomized controlled trial aims to evaluate the efficacy and safety of two different treatment durations (6-month versus 9-month regimens) regimen for patients with drug-susceptible pulmonary tuberculosis (DS-PTB) and concurrent type 2 diabetes (DM). METHODS: Patients with DS-PTB and type-2 DM from 22 hospitals in China are enrolled. They are randomized in a 1:1 ratio into either the 6-month regimen arm(2HRZE/4HR) or the 9-month regimen arm(2HRZE/7HR). At the end of the intensive phase (the 8th week), patients in both arms who with sputum positive smear will extent one more month of intensive treatment. The primary outcome is the proportion of unfavorable outcomes at 24 months after randomization. Secondary outcomes include treatment success rate at the end of treatment, proportion of recurrence at 24 months after randomization, time to recurrence after treatment completion, proportion of intensive phrase extension, occurrence of adverse events grade 3 or above during treatment. DISCUSSION: The study focuses on assessing the optimal treatment duration to maximize treatment success while minimizing recurrence and adverse events. The trial is expected to provide vital insights into the appropriate treatment duration for patients with TB-DM, aiming to reduce recurrence rates and improve overall treatment outcomes in this vulnerable population. TRAIL REGISTRATION: Chictr.org.cn, ChiCTR2100044663. Registered on March 25, 2021.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Tensins - emerging insights into their domain functions, biological roles and disease relevance.

Tensins are a family of focal adhesion proteins consisting of four members in mammals (TNS1, TNS2, TNS3 and TNS4). Their multiple domains and activities contribute to the molecular linkage between the extracellular matrix and cytoskeletal networks, as well as mediating signal transduction pathways, leading to a variety of physiological processes, including cell proliferation, attachment, migration and mechanical sensing in a cell. Tensins are required for maintaining normal tissue structures and functions, especially in the kidney and heart, as well as in muscle regeneration, in animals. This Review discusses our current understanding of the domain functions and biological roles of tensins in cells and mice, as well as highlighting their relevance to human diseases.

The use of cervical cerclage in asymptomatic twin pregnancies with cervical shortening or dilation: a twelve-year retrospective cohort study.

BACKGROUND: To identify the effect and optimal time of cervical cerclage in asymptomatic twin pregnancies with cervical shortening or dilation. METHODS: This observational retrospective study enrolled all women with asymptomatic twin pregnancies who were diagnosed with asymptomatic cervical shortening or dilation at the Second Affiliated Hospital of Wenzhou Medical University between 2010 and 2022. Women included were allocated into the cerclage group (n = 36) and the no cerclage group (n = 22). The cerclage group was further divided into the cerclage group (< 24 weeks group) and the cerclage group (24-28 weeks group) according to the time of cerclage. The no cerclage group was further divided into no cerclage group (< 24 weeks group) and no cerclage group (24-28 weeks group) according to the time of ultrasound-indicated or physical exam indicated cerclage. The rates of PTB < 24, 28, 32 and 34 weeks of gestation, maternal and neonatal outcomes were compared among the groups. RESULTS: The gestational age (GA) at delivery was higher (P = 0.005) and the interval time between the presentation of the indicated cerclage and delivery was longer in the cerclage group (P < 0.001). The rates of PTB before 28, 32, and 34 weeks of gestation, caesarean section and stillbirth were lower in the cerclage group (P < 0.05). The birthweight of the twins was higher in the cerclage group (P = 0.012). Admissions to the NICU were more frequent in pregnancies with no cerclage (P = 0.008). Subgroup analysis showed that the interval time between the presentation and delivery was longer in the cerclage group (< 24 weeks) (P < 0.001). The GA at delivery and the birthweight of the twins were significantly higher in the cerclage group (< 24 weeks) (P < 0.001). No differences were found in the GA at presentation, the GA at delivery, the interval time between the presentation to delivery and birthweight between the cerclage group (24-28 weeks group) and the control group (24-28 weeks group) (P > 0.05). CONCLUSIONS: Cerclage appears to prolong the GA at delivery and the interval time between the presentation to delivery, and may reduce the incidence of PTB before 28, 32 and 34 weeks of gestation and adverse perinatal outcomes in asymptomatic twin pregnancies with cervical shortening or dilation. Cerclage before 24 weeks of gestation showed longer GA at delivery, longer interval time between the presentation to delivery and higher birthweight of the twins. The GA at presentation, the GA at delivery, the interval time between the presentation to delivery and birthweight in women with cerclage at 24-28 weeks were similar to those in women without cerclage at 24-28 weeks.

Emerging role of toll-like receptors signaling and its regulators in preterm birth: a narrative review.

INTRODUCTION: Despite intensive research, preterm birth (PTB) rates have not decreased significantly in recent years due to a lack of understanding of the underlying causes and insufficient treatment options for PTB. We are committed to finding promising biomarkers for the treatment of PTB. METHODS: An extensive search of the literature was conducted with MEDLINE/PubMed, and in total, 151 studies were included and summarized in the present review. RESULTS: Substantial evidence supports that the infection and/or inflammatory cascade associated with infection is an early event in PTB. Toll-like receptor (TLR) is a prominent pattern recognition receptor (PRR) found on both immune and non-immune cells, including fetal membrane cells. The activation of TLR downstream molecules, followed by TLR binding to its ligand, is critical for infection and inflammation, leading to the involvement of the TLR signaling pathway in PTB. TLR ligands are derived from microbial components and molecules released by damaged and dead cells. Particularly, TLR4 is an essential TLR because of its ability to recognize lipopolysaccharide (LPS). In this comprehensive overview, we discuss the role of TLR signaling in PTB, focus on numerous host-derived genetic and epigenetic regulators of the TLR signaling pathway, and cover ongoing research and prospective therapeutic options for treating PTB by inhibiting TLR signaling. CONCLUSION: This is a critical topic because TLR-related molecules and mechanisms may enable obstetricians to better understand the physiological changes in PTB and develop new treatment and prevention strategies.

Electrocardiogram Heartbeat Classification for Arrhythmias and Myocardial Infarction.

An electrocardiogram (ECG) is a basic and quick test for evaluating cardiac disorders and is crucial for remote patient monitoring equipment. An accurate ECG signal classification is critical for real-time measurement, analysis, archiving, and transmission of clinical data. Numerous studies have focused on accurate heartbeat classification, and deep neural networks have been suggested for better accuracy and simplicity. We investigated a new model for ECG heartbeat classification and found that it surpasses state-of-the-art models, achieving remarkable accuracy scores of 98.5% on the Physionet MIT-BIH dataset and 98.28% on the PTB database. Furthermore, our model achieves an impressive F1-score of approximately 86.71%, outperforming other models, such as MINA, CRNN, and EXpertRF on the PhysioNet Challenge 2017 dataset.

Tandem Expression of a Mobile RNA and Its RNA-Binding Protein(s) Enhances Tuber Productivity in Potato.

A significant number of discoveries in past two decades have established the importance of long-distance signaling in controlling plant growth, development, and biotic and abiotic stress responses. Numerous mobile signals, such as mRNAs, proteins, including RNA-binding proteins, small RNAs, sugars, and phytohormones, are shown to regulate various agronomic traits such as flowering, fruit, seed development, and tuberization. Potato is a classic model tuber crop, and several mobile signals are known to govern tuber development. However, it is unknown if these mobile signals have any synergistic effects on potato crop improvement. Here, we employed a simple innovative strategy to test the cumulative effects of a key mobile RNA, StBEL5, and its RNA-binding proteins, StPTB1, and -6 on tuber productivity of two potato cultivars, Solanum tuberosum cv. Désirée and subspecies andigena, using a multi-gene stacking approach. In this approach, the coding sequences of StBEL5 and StPTB1/6 are driven by their respective native promoters to efficiently achieve targeted expression in phloem for monitoring tuber productivity. We demonstrate that this strategy resulted in earliness for tuberization and enhanced tuber productivity by 2-4 folds under growth chamber, greenhouse, and field conditions. This multi-gene stacking approach could be adopted to other crops, whose agronomic traits are governed by mobile macromolecules, expanding the possibilities to develop crops with improved traits and enhanced yields.

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM.

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.

Biomarkers for Pregnancy Latency Prediction after Preterm Premature Rupture of Membranes-A Systematic Review.

Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, ßhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection.

Electronic Structure and Chemical Bonding of the First-, Second-, and Third-Row-Transition-Metal Monoborides: The Formation of Quadruple Bonds in RhB, RuB, and TcB.

Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.

Predicting pulmonary tuberculosis incidence in China using Baidu search index: an ARIMAX model approach.

BACKGROUND: Existing researches have established a correlation between internet search data and the epidemics of numerous infectious diseases. This study aims to develop a prediction model to explore the relationship between the Pulmonary Tuberculosis (PTB) epidemic trend in China and the Baidu search index. METHODS: Collect the number of new cases of PTB in China from January 2011 to August 2022. Use Spearman rank correlation and interaction analysis to identify Baidu keywords related to PTB and construct a PTB comprehensive search index. Evaluate the predictive performance of autoregressive integrated moving average (ARIMA) and ARIMA with explanatory variable (ARIMAX) models for the number of PTB cases. RESULTS: Incidence of PTB had shown a fluctuating downward trend. The Spearman rank correlation coefficient between the PTB comprehensive search index and its incidence was 0.834 (P < 0.001). The ARIMA model had an AIC value of 2804.41, and the MAPE value was 13.19%. The ARIMAX model incorporating the Baidu index demonstrated an AIC value of 2761.58 and a MAPE value of 5.33%. CONCLUSIONS: The ARIMAX model is superior to ARIMA in terms of fitting and predicting accuracy. Additionally, the use of Baidu Index has proven to be effective in predicting cases of PTB.

PTB: Not just a polypyrimidine tract-binding protein.

Polypyrimidine tract-binding protein (PTB), as a member of the heterogeneous nuclear ribonucleoprotein family, functions by rapidly shuttling between the nucleus and the cytoplasm. PTB is involved in the alternative splicing of pre-messenger RNA (mRNA) and almost all steps of mRNA metabolism. PTB regulation is organ-specific; brain- or muscle-specific microRNAs and long noncoding RNAs partially contribute to regulating PTB, thereby modulating many physiological and pathological processes, such as embryonic development, cell development, spermatogenesis, and neuron growth and differentiation. Previous studies have shown that PTB knockout can inhibit tumorigenesis and development. The knockout of PTB in glial cells can be reprogrammed into functional neurons, which shows great promise in the field of nerve regeneration but is controversial.