Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35-762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Alternative polyadenylation regulates the translation of metabolic and inflammation-related proteins in adipose tissue of gestational diabetes mellitus.

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

A preliminary, quantitative study on the use of traditional and complementary medicine by cancer patients seen at the Senkatana oncology clinic, Maseru, Lesotho.

BACKGROUND: The use of traditional and complementary medicine (TCM) by cancer patients remains common in several countries especially in the Sub-Saharan Africa. However, the reasons for use are complex and change with time and geographic location, they may vary from therapy to therapy, and they are different from one individual to another. The use of TCM has been associated with active coping behaviour and a way through which patients take control of their own health. However, cancer patients do not disclose their use of TCM to the attending healthcare professionals and therefore the effects of these medicines on the patients may not be ascertained. AIM: To investigate the use of traditional and complementary medicines among patients diagnosed with cancer. METHODS: A cross-sectional, quantitative study was conducted at Senkatana Oncology clinic in May to June 2023. Cancer patients underwent standardized, quantitative interviews using structured questionnaires about their use of TCM. Descriptive statistics were used to analyse the data. Logistic regression analysis was also used to identify factors associated with satisfaction with the performance of TCM. RESULTS: All interviewed patients (n = 50, 100%) reported to be using TCM. Patients consisted of 24 females (48%) and 26 males (52%) in the age range 14 to 82 years old. The majority of the study population was in the age group 35-44 years old. The most prevalent cancer among participating males was prostate cancer and among females was cervical cancer. Biological products use was the most prominent with the highest average percentage usage (14.7%). The majority of patients (66%, n = 33) indicated that they just wanted to try everything that could help. Patients (n = 47, 94%) further reported that they had been using complementary medicine during the same period as they were using conventional treatment so that both may work to help each other. Neither gender nor age predicted satisfaction with the performance of traditional and complementary medicine. CONCLUSIONS: It is concluded that all interviewed cancer patients use TCM. Patients indicated that one of the reasons for using TCM was that they wanted to try everything that could help in their cancer care. Patients further reported that they did not inform their oncologist of their concurrent use of TCM because they had been advised not to use other medicines besides what they are given at the clinic.

Combining various acupuncture therapies with multimodal analgesia to enhance postoperative pain management following total knee arthroplasty: a network meta-analysis of randomized controlled trials.

Objective: This study aims to evaluate the efficacy and safety of various acupuncture treatments in conjunction with multimodal analgesia (MA) for managing postoperative pain and improving knee function in patients undergoing total knee arthroplasty (TKA), based on the findings from clinical research indicating the potential benefits of acupuncture-related therapies in this context. Methods: We searched Web of Science, PubMed, SCI-hub, Embase, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials of acupuncture-related therapies for post-TKA pain. After independent screening and data extraction, the quality of the included literature was evaluated. The potential for bias in the studies incorporated in the analysis was assessed according to the guidelines outlined in the Cochrane Handbook 5.1. Network meta-analysis (NMA) was conducted using RevMan 5.4 and Stata 16.0 software, with primary outcome measures including visual analog scale (VAS), pain pressure threshold (PPT), hospital for special surgery knee score (HSS), and knee joint range of motion (ROM). Furthermore, the interventions were ranked based on the SUCRA value. Results: We conducted an analysis of 41 qualifying studies encompassing 3,003 patients, examining the efficacy of four acupuncture therapies (acupuncture ACU, electroacupuncture EA, transcutaneous electrical acupoint stimulation TEAS, and auricular acupoint therapy AAT) in conjunction with multimodal analgesia (MA) and MA alone. The VAS results showed no significant difference in efficacy among the five interventions for VAS-3 score. However, TEAS+MA (SMD: 0.67; 95%CI: 0.01, 1.32) was more effective than MA alone for VAS-7 score. There was no significant difference in PPT score among the three interventions. ACU + MA (SMD: 6.45; 95%CI: 3.30, 9.60), EA + MA (SMD: 4.89; 95%CI: 1.46, 8.32), and TEAS+MA (SMD: 5.31; 95%CI: 0.85, 9.78) were found to be more effective than MA alone for HSS score. For ROM score, ACU + MA was more efficacious than EA + MA, TEAS+MA, and AAT + MA, MA. Regarding the incidence of postoperative adverse reactions, nausea and vomiting were more prevalent after using only MA. Additionally, the incidence of postoperative dizziness and drowsiness following ACU + MA (OR = 4.98; 95%CI: 1.01, 24.42) was observed to be higher compared to that after AAT + MA intervention. Similarly, the occurrence of dizziness and drowsiness after MA was found to be significantly higher compared to the following interventions: TEAS+MA (OR = 0.36; 95%CI: 0.18, 0.70) and AAT + MA (OR = 0.20; 95%CI: 0.08, 0.50). The SUCRA ranking indicated that ACU + MA, EA + MA, TEAS+MA, and AAT + MA displayed superior SUCRA scores for each outcome index, respectively. Conclusion: For the clinical treatment of post-TKA pain, acupuncture-related therapies can be selected as a complementary and alternative therapy. EA + MA and TEAS+MA demonstrate superior efficacy in alleviating postoperative pain among TKA patients. ACU + MA is the optimal choice for promoting postoperative knee joint function recovery in TKA patients. AAT + MA is recommended for preventing postoperative adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/, identifier (CRD42023492859).

Activation of Cryptic Donor Splice Sites Within the UGT1A First-Exon Region Generates Variant Transcripts That Encode UGT1A Proteins With Truncated Aglycone-binding Domains.

The human UDP-glucuronosyltransferases (UGTs) have crucial roles in metabolizing and clearing numerous small lipophilic compounds. The UGT1A locus generates nine UGT1A mRNAs, 65 spliced transcripts and 34 circular RNAs. In this study, our analysis of published UGT-CaptureSeq datasets identified novel splice junctions that predict 24 variant UGT1A transcripts derived from ligation of exon 2 to unique sequences within the UGT1A first-exon region using cryptic donor splice sites. Of these variants, seven (1A1_n1, 1A3_n3, 1A4_n4, 1A5_n1, 1A8_n2, 1A9_n2v, 1A10_n7) are predicted to encode UGT1A proteins with truncated aglycone-binding domains. We assessed their expression profiles and deregulation in cancer using four RNA-seq datasets of paired normal and cancerous drug-metabolizing tissues from large patient cohorts. Variants were generally co-expressed with their canonical counterparts with a higher relative abundance in tumor than in normal tissues. Variants showed tissue-specific expression with high interindividual variability but overall low abundance. However, 1A8_n2 showed high abundance in normal and cancerous colorectal tissues with levels that approached or surpassed canonical 1A8 mRNA levels in many samples. We cloned 1A8_n2 and showed expression of the predicted protein (1A8_i3) in HEK293T cells. Glucuronidation assays with 4-MU showed that 1A8_i3 had no activity and was unable to inhibit the activity of 1A8_i1 protein. In summary, the activation of cryptic donor splice sites within the UGT1A first-exon region expands the UGT1A transcriptome and proteome. The 1A8_n2 cryptic donor splice site is highly active in colorectal tissues, representing an important cis-regulatory element that negatively regulates the function of the UGT1A8 gene through pre-mRNA splicing. Significance Statement The UGT1A locus generates nine canonical mRNAs, 65 alternately spliced transcripts and 34 different circular RNAs. The present study reports a series of novel UGT1A variants resulting from use of cryptic donor splice sites in both normal and cancerous tissues, several of which are predicted to encode variant UGT1A proteins with truncated aglycone-binding domains. Of these, 1A8_n2 shows exceptionally high abundance in colorectal tissues, highlighting its potential role in the first-pass metabolism in gut through the glucuronidation pathway.

Gaseous ozone and ozonized mist in the control of Escherichia coli on 'Rama Forte' persimmon.

This study aimed to evaluate the effectiveness of using two ozone applications (gaseous and mist) as a disinfection method for fresh persimmon. To test these sanitizers, in vitro and in vivo assays were performed, and the Escherichia coli was selected because it is a pathogen that causes foodborne diseases in humans. For in vitro experiments, a plate was inoculated with Escherichia coli strain ATCC 25922 and treated. For in vivo assays, persimmon fruit surface was inoculated with the bacteria and treated. For both assays, it was used 10,15,20,30,40 and 50 µL L-1 of gaseous ozone or ozonized mist for five minutes. The results demonstrated that the gas ozone application significantly reduced the growth of E. coli on the plate surface in vitro at doses of 30, 40 and 50 µL L-1 (with 0.83, 0.89 and 0.95 log CFU mL-1, respectively). The application of ozonized mist showed a significant reduction for 50 µL L-1 (with 1.28 log CFU g-1). And, for the in vivo assays, ozonized mist significantly reduced the number of bacteria on the persimmon surface, with a 1.57 log reduction, which was the largest for 40 µL L-1. Therefore, it is possible to conclude that the ozone application can contribute to the control of microorganisms present on fruit surfaces.

The use of biofield energy therapy as complementary and alternative medicine in human health care system: a narrative review and potential mechanisms.

INTRODUCTION: There has been accumulating interest in the application of biofield therapy as complementary and alternative medicine (CAM) to treat various diseases. The practices include reiki, qigong, blessing, prayer, distant healing, known as biofield therapies. This paper aims to state scientific knowledge on preclinical and clinical studies to validate its potential use as an alternative medicine in the clinic. It also provides a more in-depth context for understanding the potential role of quantum entanglement in the effect of biofield energy therapy. CONTENT: A comprehensive literature search was performed using the different databases (PubMed, Scopus, Medline, etc.). The published English articles relevant to the scope of this review were considered. The review gathered 45 papers that were considered suitable for the purpose. Based on the results of these papers, it was concluded that biofield energy therapy was effective in treating different disease symptoms in preclinical and clinical studies. SUMMARY: Biofield therapies offer therapeutic benefits for different human health disorders, and can be used as alternative medicine in clinics for the medically pluralistic world due to the growing interest in CAM worldwide. OUTLOOK: The effects of the biofield energy therapies are observed due to the healer's quantum thinking, and transmission of the quantum energy to the subject leads to the healing that occurs spiritually through instantaneous communication at the quantum level via quantum entanglement.

Identification, diversity, and evolution analysis of Commd gene family in Haliotis discus hannai and immune response to biotic and abiotic stresses.

The Commd (Copper Metabolism gene MURR1 Domain) family genes play crucial roles in various biological processes, including copper and sodium transport regulation, NF-κB activity, and cell cycle progression. Their function in Haliotis discus hannai, however, remains unclear. This study focused on identifying and analyzing the Commd genes in H. discus hannai, including their gene structure, phylogenetic relationships, expression profiles, sequence diversity, and alternative splicing. The results revealed significant homology between H. discus hannai's Commd genes and those of other mollusks. Both transcriptome quantitative analysis and qRT-PCR demonstrated the responsiveness of these genes to heat stress and Vibrio parahaemolyticus infection. Notably, alternative splicing analysis revealed that COMMD2, COMMD4, COMMD5, and COMMD7 produce multiple alternative splice variants. Furthermore, sequence diversity analysis uncovered numerous missense mutations, specifically 9 in COMMD5 and 14 in COMMD10. These findings contribute to expanding knowledge on the function and evolution of the Commd gene family and underscore the potential role of COMMD in the innate immune response of H. discus hannai. This research, therefore, offers a novel perspective on the molecular mechanisms underpinning the involvement of Commd genes in innate immunity, paving the way for further explorations in this field.

Water-soluble microencapsulation using gum Arabic and skim milk enhances viability and efficacy of Pediococcus acidilactici probiotic strains for application in broiler chickens.

Objective: This study aimed to develop and evaluate the effectiveness of a water-soluble microencapsulation method for probiotic strains using gum Arabic (GA) and skim milk (SKM) over a three-month storage period following processing. Methods: Four strains of Pediococcus acidilactici (BYF26, BYF20, BF9, and BF14) that were typical lactic acid bacteria (LAB) isolated from the chicken gut were mixed with different ratios of gum Arabic (GA) and skim milk (SKM) as coating agents before spray drying at an inlet temperature 140°C. After processing, the survivability and probiotic qualities of the strains were assessed from two weeks to three months of storage at varied temperatures, and de-encapsulation was performed to confirm the soluble properties. Finally, the antibacterial activity of the probiotics was assessed under simulated gastrointestinal conditions. Results: As shown by scanning electron microscopy, spray-drying produced a spherical, white-yellow powder. The encapsulation efficacy (EE percent) was greatest for a coating containing a combination of 30% gum Arabic: 30% skim milk (w/v) (GA:SKM30) compared to lower concentrations of the two ingredients (p<0.05). Coating with GA:SKM30 (w/v) significantly enhanced (p<0.05) BYF26 survival under simulated gastrointestinal conditions (pH 2.5-3) and maintained higher survival rates compared to non-encapsulated cells under an artificial intestinal juices (AIJ) condition of pH 6. De-encapsulation tests indicated that the encapsulated powder dissolved in water while keeping viable cell counts within the effective range of 106 for 6 hours. In addition, following three months storage at 4°C, microencapsulation of BYF26 in GA:SKM30 maintained both the number of viable cells (p<0.05) and the preparation's antibacterial efficacy against pathogenic bacteria, specifically strains of Salmonella. Conclusion: Our prototype water-soluble probiotic microencapsulation GA:SKM30 effectively maintains LAB characteristics and survival rates, demonstrating its potential for use in preserving probiotic strains that can be used in chickens and potentially in other livestock.

A scoping review of AAC interventions for children and young adults with simultaneous visual and motor impairments: Clinical and research Implications.

Individuals with multiple disabilities are among the most challenging to serve and AAC teams often lack direction in determining effective interventions. The purpose of this scoping review was to summarize the research evidence on AAC interventions for individuals with complex communication needs and simultaneous motor, and visual impairments as part of their multiple disabilities; to consider implications for practice; and to determine gaps and directions for future research. A total of 27 studies were identified and reviewed, involving 55 unique participants with multiple disabilities. Most studies focused on direct intervention to increase requesting or choice-making, with little focus on social communication. Only two studies focused on training communication partners. Results indicated that AAC interventions can be highly effective to increase communication for individuals with multiple disabilities. However, there is an urgent need for increased rigor and more detailed participant information in future AAC intervention research with this population. Future research should investigate AAC intervention to improve social communication and increase language development, not just expression of needs and wants. Future research should focus on the needs of individuals with multiple disabilities from culturally and linguistically diverse backgrounds and on implementation of AAC within natural environments.

Effects of an integrative multimodal inpatient program on fatigue and work ability in patients with Post-COVID Syndrome-a prospective observational study.

Post-COVID syndrome (PCS) is characterized by a variety of non-specific symptoms. One of the leading symptoms is fatigue. So far, there is no evidence-based causal therapy established and treatment of PCS is primarily symptom-oriented. The Clinic for Internal and Integrative Medicine in Bamberg, Germany, offers a comprehensive multimodal integrative inpatient therapy for PCS patients. Within a prospective uncontrolled observational study, the results of N = 79 patients were analysed. Post-COVID fatigue patients were hospitalized for up to 14 days. The treatment consists of individual modules depending on the patient's needs. It includes a wide range of integrative non-pharmacological treatment modalities. Outcomes were assessed before and after the inpatient treatment as well as 6 months after discharge from the hospital. Results show that fatigue of post-COVID patients in this study (M = 76.30, SD = 10.18, N = 64) was initially significantly higher than in the subsample "women aged 60-92 years" of the general German population (M = 51.5, Schwarz et al. [Schwarz et al. in Onkologie 26:140-144, 2003]; T(63) = 19.50, p < .001). Fatigue was significantly and clinically relevant reduced directly after discharge (MT1 = 76.21, SD = 11.38, N = 42; MT2 = 66.57, SD = 15.55, N = 42), F(1, 41) = 19.80, p < .001, partial eta squared = .326, as well as six months after discharge (MT3 = 65.31, SD = 17.20, N = 42), F(1, 41), p < .001, partial eta squared = .371. Additionally, self-reported ability to work (NRS, 0-10) improved significantly from admission (MT1 = 2.54, SD = 2.23, N = 39) to discharge (MT2 = 4.26, SD = 2.60, N = 39), F(1, 38) = 26.37, p < .001, partial eta squared = .410), as well as to six months later (MT3 = 4.41, SD = 3.23, N = 39), F(1, 38) = 15.00, p < .001, partial eta squared = .283. The study showed that patients suffering from chronic post-COVID syndrome for several months can achieve a significant improvement in their leading fatigue symptoms and a significant improvement in the subjective assessment of their ability to work through a comprehensive two-week multimodal integrative inpatient program.

A pediatric case of atypical hemolytic uremic syndrome (aHUS): Could any infection play a triggering role?

A 12-year-old boy was transferred to our pediatric department from a rural hospital for fever, cough, and vomiting associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury, leading to the diagnosis of hemolytic uremic syndrome (HUS). A nasopharyngeal swab and a lower respiratory sample detected Influenza A by polymerase chain reaction (PCR). The patient was treated with oseltamivir and intravenous fluids in addition to fresh frozen plasma (FFP). Enteropathogenic Escherichia coli (EPEC) was detected in a stool sample by PCR. Serum antibodies for Mycoplasma pneumoniae (IgM and IgG) and Helicobacter pylori (IgA and IgG) were increased. Further work-up revealed elevated serum C5b-9 suggesting a simultaneous viral and bacterial infection-mediated complement overactivation leading to the diagnosis of atypical HUS (aHUS). An association between aHUS and influenza A is reported in the literature, but the correlation of EPEC, Mycoplasma pneumoniae, and Helicobacter pylori with aHUS is not well-established. Fresh frozen plasma was administered for a total of 3 days, followed by clinical and laboratory improvement. The patient has remained asymptomatic until the latest follow-up, 5 months after discharge. This case demonstrates the potential triggering role of different pathogens in aHUS pathogenesis to raise awareness in the pediatric community.

The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing.

Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Altered phosphorylation endows LB-100-treated colorectal adenocarcinoma cells with differential splicing patterns. In PP2A-inhibited cells, over 1000 events of exon skipping and intron retention affect regulators of genomic integrity. Finally, we show that LB-100-evoked alternative splicing leads to neoantigens that are presented by MHC class 1 at the cell surface. Our findings provide a potential explanation for the pre-clinical and clinical observations that LB-100 sensitizes cancer cells to immune checkpoint blockade.

BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.

The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.

Transcriptomic analysis of differentially alternative splicing patterns in mice with inflammatory and neuropathic pain.

Although the molecular mechanisms of chronic pain have been extensively studied, a global picture of alternatively spliced genes and events in the peripheral and central nervous systems of chronic pain is poorly understood. The current study analyzed the changing pattern of alternative splicing (AS) in mouse brain, dorsal root ganglion, and spinal cord tissue under inflammatory and neuropathic pain. In total, we identified 6495 differentially alternatively spliced (DAS) genes. The molecular functions of shared DAS genes between these two models are mainly enriched in calcium signaling pathways, synapse organization, axon regeneration, and neurodegeneration disease. Additionally, we identified 509 DAS in differentially expressed genes (DEGs) shared by these two models, accounting for a small proportion of total DEGs. Our findings supported the hypothesis that the AS has an independent regulation pattern different from transcriptional regulation. Taken together, these findings indicate that AS is one of the important molecular mechanisms of chronic pain in mammals. This study presents a global description of AS profile changes in the full path of neuropathic and inflammatory pain models, providing new insights into the underlying mechanisms of chronic pain and guiding genomic clinical diagnosis methods and rational medication.

Utilization of used textiles for solid recovered fuel production.

One of the current important issues is the management of used textiles. One method is recycling, but the processes are characterized by a high environmental burden and the products obtained are of lower quality. Used textiles can be successfully used to produce SRF (solid recovered fuels). This type of fuel is standardized by ISO 21640:2021. In the paper, an analysis of used textiles made from fibers of different origins was performed. These were acrylic, cotton, linen, polyester, wool, and viscose. A proximate and ultimate analysis of the investigated samples was performed, including mercury and chlorine content. The alternative fuel produced from used textiles will be characterized by acceptable parameters for consumers: a lower heating value at 20 MJ/kg (class 1-3 SRF), mercury content below 0.9 µg Hg/MJ (class 1 SRF), and a chlorine content below 0.2% (class 1 SRF). However, the very high sulfur content in wool (3.0-3.6%) and the high nitrogen content in acrylic may limit its use for power generation. The use of alternative fuel derived from used textiles may allow 3% of the coal consumed to be substituted in 2030. The reduction in carbon dioxide emissions from the substitution of coal with an alternative fuel derived from used textiles will depend on their composition. For natural and man-made cellulosic fibers, the emission factor can be assumed as for plant biomass, making their use for SRF production preferable. For synthetic fibers, the emission factor was estimated at the level of 102 and 82 gCO2/MJ for polyester and acrylic, respectively.

Aberrant splicing of CaV1.2 calcium channel induced by decreased Rbfox1 enhances arterial constriction during diabetic hyperglycemia.

Diabetic hyperglycemia induces dysfunctions of arterial smooth muscle, leading to diabetic vascular complications. The CaV1.2 calcium channel is one primary pathway for Ca2+ influx, which initiates vasoconstriction. However, the long-term regulation mechanism(s) for vascular CaV1.2 functions under hyperglycemic condition remains unknown. Here, Sprague-Dawley rats fed with high-fat diet in combination with low dose streptozotocin and Goto-Kakizaki (GK) rats were used as diabetic models. Isolated mesenteric arteries (MAs) and vascular smooth muscle cells (VSMCs) from rat models were used to assess K+-induced arterial constriction and CaV1.2 channel functions using vascular myograph and whole-cell patch clamp, respectively. K+-induced vasoconstriction is persistently enhanced in the MAs from diabetic rats, and CaV1.2 alternative spliced exon 9* is increased, while exon 33 is decreased in rat diabetic arteries. Furthermore, CaV1.2 channels exhibit hyperpolarized current-voltage and activation curve in VSMCs from diabetic rats, which facilitates the channel function. Unexpectedly, the application of glycated serum (GS), mimicking advanced glycation end-products (AGEs), but not glucose, downregulates the expression of the splicing factor Rbfox1 in VSMCs. Moreover, GS application or Rbfox1 knockdown dynamically regulates alternative exons 9* and 33, leading to facilitated functions of CaV1.2 channels in VSMCs and MAs. Notably, GS increases K+-induced intracellular calcium concentration of VSMCs and the vasoconstriction of MAs. These results reveal that AGEs, not glucose, long-termly regulates CaV1.2 alternative splicing events by decreasing Rbfox1 expression, thereby enhancing channel functions and increasing vasoconstriction under diabetic hyperglycemia. This study identifies the specific molecular mechanism for enhanced vasoconstriction under hyperglycemia, providing a potential target for managing diabetic vascular complications.

Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.

Escaping from CRISPR-Cas-mediated knockout: the facts, mechanisms, and applications.

Clustered regularly interspaced short palindromic repeats and associated Cas protein (CRISPR-Cas), a powerful genome editing tool, has revolutionized gene function investigation and exhibits huge potential for clinical applications. CRISPR-Cas-mediated gene knockout has already become a routine method in research laboratories. However, in the last few years, accumulating evidences have demonstrated that genes knocked out by CRISPR-Cas may not be truly silenced. Functional residual proteins could be generated in such knockout organisms to compensate the putative loss of function, termed herein knockout escaping. In line with this, several CRISPR-Cas-mediated knockout screenings have discovered much less abnormal phenotypes than expected. How does knockout escaping happen and how often does it happen have not been systematically reviewed yet. Without knowing this, knockout results could easily be misinterpreted. In this review, we summarize these evidences and propose two main mechanisms allowing knockout escaping. To avoid the confusion caused by knockout escaping, several strategies are discussed as well as their advantages and disadvantages. On the other hand, knockout escaping also provides convenient tools for studying essential genes and treating monogenic disorders such as Duchenne muscular dystrophy, which are discussed in the end.

The Use of Solid Sodium Silicate as Activator for an Amorphous Wollastonitic Hydraulic Binder.

To ensure the acceptable mechanical strength of amorphous wollastonitic hydraulic binders (AWHs), activation with a sodium silicate solution is necessary. However, the use of this type of activator increases the final cost and the complexity of the product's overall use. In this work, we focus on enhancing the manufacturing of the alkaline activator by producing three Na2SiO3 powders using cost-effective raw materials. The procedure consisted of heating a mixture of NaOH pebbles with either sand, glass, or diatomite to a temperature of 330 °C for 2 h. After synthesis, the powders were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Diffraction (XRD) techniques. Finally, mortars made with AWHs were activated using the synthesized powders that were added either as a solid or dissolved in an aqueous solution. The compressive strength results in these mortars show that the lab-made activators are competitive with the traditional sodium silicate activators. Furthermore, the synthetized activators can be added in either solid form or pre-dissolved in a solution. This innovative approach represents a more economical, sustainable and easy-to-use approach to enhancing the competitiveness of AWHs.