Synthesis of highly luminescent core-shell nanoprobes in a single pot for ofloxacin detection in blood serum and water.

Antibiotics are commonly used as antibacterial medications due to their extensive and potent therapeutic properties. However, the overconsumption of these chemicals leads to their accumulation in the human body via the food chain, amplifying drug resistance and compromising immunity, thus presenting a significant hazard to human health. Antibiotics are classified as organic pollutants. Therefore, it is crucial to conduct research on precise methodologies for detecting antibiotics in many substances, including food, pharmaceutical waste, and biological samples like serum and urine. The methodology described in this research paper introduces an innovative technique for producing nanoparticles using silica as the shell material, iron oxide as the core material, and carbon as the shell dopant. By integrating a carbon-doped silica shell, this substance acquires exceptional fluorescence characteristics and a substantial quantum yield value of 80%. By capitalising on this characteristic of the substance, we have effectively constructed a fluorescent sensor that enables accurate ofloxacin analysis, with a detection limit of 1.3 × 10-6 M and a linear range of concentrations from 0 to 120 × 10-6 M. We also evaluated the potential of CSIONPs for OLF detection in blood serum and tap water analysis. The obtained relative standard deviation values were below 3.5%. The percentage of ofloxacin recovery from blood serum ranged from 95.52% to 103.28%, and from 89.9% to 96.0% from tap water.

Reshaping the equitable and inclusive access to healthcare: A qualitative study.

Background: Improving equitable access to healthcare requires innovative interventions and strengthening a service innovation operational model to achieve transformative change and bring sustainability to public health interventions. The current study aims to identify the components of the Mobile Medical Units (MMUs) operational model as an innovative intervention to provide equitable and inclusive access to healthcare. Methods: The study used qualitative research to identify the components of the operational model of MMUs for primary healthcare in future. Data has been collected via semi-structured in-depth interviews with 103 healthcare professionals from six states representing India's Tier I, Tier II, and Tier III regions. A thematic analysis was performed to examine emergent salient themes. Results: The study identified and examined scalability, affordability, replicability, and sustainability as the four critical components of the operational model of MMUs. The findings of the study indicated that MMUs with these four components played a vital role in COVID-19 immunization, especially in resource-limited settings. The study found that MMUs are a cost-effective and scalable healthcare delivery model that can be easily replicated in primary healthcare service delivery. Conclusion: The findings underscore the significant role of MMUs in addressing healthcare disparities, particularly in resource-limited settings. The adaptability and cost-effectiveness of MMUs make them an ideal solution for primary healthcare delivery, especially in Tier I, II, and III regions of India. It lays a foundation for future research and policy-making, emphasizing the need for innovative, equitable, and sustainable healthcare delivery models like MMUs to transform and strengthen healthcare systems globally.

In vitro effects of alginate lyase SG4 + produced by Paenibacillus lautus alone and combined with antibiotics on biofilm formation by mucoid Pseudomonas aeruginosa.

Alginate is a major extra polymeric substance in the biofilm formed by mucoid Pseudomonas aeruginosa. It is the main proven perpetrator of lung infections in patients suffering from cystic fibrosis. Alginate lyases are very important in the treatment of cystic fibrosis. This study evaluated the role of standalone and in conjugation, effect of alginate lyase of SG4 + isolated from Paenibacillus lautus in enhancing in vitro bactericidal activity of gentamicin and amikacin on mucoid P. aeruginosa. Using Response Surface Methodology (RSM) alginate lyase SG4 + production was optimized in shake flask and there 8.49-fold enhancement in enzyme production. In fermenter, maximum growth (10.15 mg/ml) and alginate lyase (1.46 International Units) production, 1.71-fold was increased using Central Composite Design (CCD). Further, fermentation time was reduced from 48 to 20 h. To the best of our knowledge this is the first report in which CCD was used for fermenter studies to optimize alginate lyase production. The Km and Vmax of purified enzyme were found to be 2.7 mg/ml and 0.84 mol/ml-min, respectively. The half-life (t 1/2) of purified alginate lyase SG4 + at 37 °C was 180 min. Alginate lyase SG4 + in combination with gentamicin and amikacin eradiated 48.4- 52.3% and 58- 64.6%, alginate biofilm formed by P. aeruginosa strains, respectively. The study proves that alginate lyase SG4 + has excellent exopolysaccharide disintegrating ability and may be useful in development of potent therapeutic agent to treat P. aeruginosa biofilms.

A deep catalogue of protein-coding variation in 983,578 individuals.

Rare coding variants that significantly impact function provide insights into the biology of a gene1-3. However, ascertaining their frequency requires large sample sizes4-8. Here, we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. 23% of the Regeneron Genetics Center Million Exome data (RGC-ME) comes from non-European individuals of African, East Asian, Indigenous American, Middle Eastern, and South Asian ancestry. This catalogue includes over 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss-of-function, we identify 3,988 loss-of-function intolerant genes, including 86 that were previously assessed as tolerant and 1,153 lacking established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions depleted of missense variants despite being tolerant to pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this important resource of coding variation from the RGC-ME accessible via a public variant allele frequency browser.

Nanostructured Biopolymer-Based Constructs for Cartilage Regeneration: Fabrication Techniques and Perspectives.

The essential functions of cartilage, such as shock absorption and resilience, are hindered by its limited regenerative capacity. Although current therapies alleviate symptoms, novel strategies for cartilage regeneration are desperately needed. Recent developments in three-dimensional (3D) constructs aim to address this challenge by mimicking the intrinsic characteristics of native cartilage using biocompatible materials, with a significant emphasis on both functionality and stability. Through fabrication methods such as 3D printing and electrospinning, researchers are making progress in cartilage regeneration; nevertheless, it is still very difficult to translate these advances into clinical practice. The review emphasizes the importance of integrating various fabrication techniques to create stable 3D constructs. Meticulous design and material selection are required to achieve seamless cartilage integration and durability. The review outlines the need to address these challenges and focuses on the latest developments in the production of hybrid 3D constructs based on biodegradable and biocompatible polymers. Furthermore, the review acknowledges the limitations of current research and provides perspectives on potential avenues for effectively regenerating cartilage defects in the future.

The Role of Phytonutrient Kaempferol in the Prevention of Gastrointestinal Cancers: Recent Trends and Future Perspectives.

In recent years, kaempferol, a natural flavonoid present in various fruits and vegetables, has received significant attention in gastrointestinal cancer research due to its varied therapeutic effects. Kaempferol has been proven to alter several molecular mechanisms and pathways, such as the PI3/Akt, mTOR, and Erk/MAPK pathway involved in cancer progression, showing its inhibitory effects on cell proliferation, survival, angiogenesis, metastasis, and migration. Kaempferol is processed in the liver and small intestine, but limited bioavailability has been a major concern in the clinical implications of kaempferol. Nano formulations have been proven to enhance kaempferol's efficacy in cancer prevention. The synergy of nanotechnology and kaempferol has shown promising results in in vitro studies, highlighting the importance for more in vivo research and clinical trials to determine safety and efficacy. This review aims to focus on the role of kaempferol in various types of gastrointestinal cancer and how the combination of kaempferol with nanotechnology helps in improving therapeutic efficacy in cancer treatment.

Appraising LaQshya's potential in measuring quality of care for mothers and newborns: a comprehensive review of India's Labor Room Quality Improvement Initiative.

BACKGROUND: Poor intrapartum care in India contributes to high maternal and newborn mortality. India's Labor Room Quality Improvement Initiative (LaQshya) launched in 2017, aims to improve intrapartum care by minimizing complications, enforcing protocols, and promoting respectful maternity care (RMC). However, limited studies pose a challenge to fully examine its potential to assess quality of maternal and newborn care. This study aims to bridge this knowledge gap and reviews LaQshya's ability to assess maternal and newborn care quality. Findings will guide modifications for enhancing LaQshya's effectiveness. METHODS: We reviewed LaQshya's ability to assess the quality of care through a two-step approach: a comprehensive descriptive analysis using document reviews to highlight program attributes, enablers, and challenges affecting LaQshya's quality assessment capability, and a comparison of its measurement parameters with the 352 quality measures outlined in the WHO Standards for Maternal and Newborn Care. Comparing LaQshya with WHO standards offers insights into how its measurement criteria align with global standards for assessing maternity and newborn care quality. RESULTS: LaQshya utilizes several proven catalysts to enhance and measure quality- institutional structures, empirical measures, external validation, certification, and performance incentives for high-quality care. The program also embodies contemporary methods like quality circles, rapid improvement cycles, ongoing facility training, and plan-do-check, and act (PDCA) strategies for sustained quality enhancement. Key drivers of LaQshya's assessment are- leadership, staff mentoring, digital infrastructure and stakeholder engagement from certified facilities. However, governance issues, understaffing, unclear directives, competency gaps, staff reluctance towards new quality improvement approaches inhibit the program, and its capacity to enhance quality of care. LaQshya addresses 76% of WHO's 352 quality measures for maternal and newborn care but lacks comprehensive assessment of crucial elements: harmful labor practices, mistreatment of mothers or newborns, childbirth support, and effective clinical leadership and supervision. CONCLUSION: LaQshya is a powerful model for evaluating quality of care, surpassing other global assessment tools. To achieve its maximum potential, we suggest strengthening district governance structures and offering tailored training programs for RMC and other new quality processes. Furthermore, expanding its quality measurement metrics to effectively assess provider accountability, patient outcomes, rights, staff supervision, and health facility leadership will increase its ability to assess quality improvements.

Self-propelling bacteria-based magnetic nanoparticles (BacMags) for targeted magnetic hyperthermia therapy against hypoxic tumors.

Magnetic hyperthermia-based cancer therapy (MHCT) holds great promise as a non-invasive approach utilizing heat generated by an alternating magnetic field for effective cancer treatment. For an efficacious therapeutic response, it is crucial to deliver therapeutic agents selectively at the depth of tumors. In this study, we present a new strategy using the naturally occurring tumor-colonizing bacteria Escherichia coli (E. coli) as a carrier to deliver magnetic nanoparticles to hypoxic tumor cores for effective MHCT. Self-propelling delivery agents, "nano-bacteriomagnets" (BacMags), were developed by incorporating anisotropic magnetic nanocubes into E. coli which demonstrated significantly improved hyperthermic performance, leading to an impressive 85% cell death in pancreatic cancer. The in vivo anti-cancer response was validated in a syngeneic xenograft model with a 50% tumor inhibition rate within 20 days and a complete tumor regression within 30 days. This proof-of-concept study demonstrates the potential of utilizing anaerobic bacteria for the delivery of magnetic nanocarriers as a smart therapeutic approach for enhanced MHCT.

Ultrasensitive NIR fluorometric assay for inorganic pyrophosphatase detection via Cu2+-PPi interaction using bimetallic Au-Ag nanoclusters.

BACKGROUND: Inorganic pyrophosphatase (PPase) is key enzyme playing a key role in biochemical transformations such as biosynthesis of DNA and RNA, bone formation, metabolic pathways associated with lipid, carbohydrate and phosphorous. It has been reported that lung adenocarcinomas, colorectal cancer, and hyperthyroidism disorders can result from abnormal level of PPase. Therefore, it is of notable significance to develop simple and effective real time assay for PPase enzyme activity monitoring for screening of many metabolic pathways as well as for early disease diagnosis. RESULT: The fluorometric detection of PPase enzyme in near infrared region-1 (NIR-1) has been carried out using bimetallic nanoclusters (LA@AuAg NCs). The developed sensing strategy was based on quenching of fluorescence intensity of LA@AuAg NCs upon interaction with copper (Cu2+) ions. The off state of LA@AuAg_Cu2+ ensemble was turned on upon addition of pyrophosphate anion (PPi) due to strong binding interaction between PPi and Cu2+. The catalytic conversion of PPi into phosphate anion (Pi) in the presence of PPase led to liberation of Cu2+ ions, and again quenched off state was retrieved due to interaction of free Cu2+ with LA@AuAg NCs. The ultrasensitive detection of PPase was observed in the linear range of 0.06-250 mU/mL with LOD as 0.0025 mU/mL. The designed scheme showed good selectivity towards PPase enzyme in comparison to other bio-substrates, along with good percentage recovery for PPase detection in real human serum samples. SIGNIFICANCE: The developed NIR based assay is ultrasensitive, highly selective and robust for PPase enzyme and can be safely employed for other enzymes detection. This highly sensitive nature of biosensor was result of involvement of fluorescence-based technique and synergistic effect of dual metal in NIR based bimetallic NCs. Moreover, owing to the emission in NIR domain, in future, these nanoclusters can be safely employed for many biomedical applications for In vivo studies.

GripAble: Interrater reliability and normative grip strength of UK population.

BACKGROUND: Hand grip strength is an established indicator of individual health status and is used as a biomarker for predicting mortality, disability, and disease risks. GripAble hand grip dynamometer offers a modernized approach to measuring grip strength with its digital and high-accuracy measurement system. PURPOSE: This study aimed to (1) assess the interrater reliability of maximum grip strength (MGS) measurement and (2) establish GripAble's own gender-, age group- and hand-stratified normative MGS reference values of the adult UK population. STUDY DESIGN: Cross-sectional study design. METHODS: Interrater reliability among three raters assessing 30 participants across diverse age groups was measured using the intraclass correlation. In the second study, 11 investigators gathered MGS data from 907 participants across diverse age groups and gender. The average, standard deviation, minimum, median, maximum, and percentiles of MGS were computed for each gender, age group, and hand (L/R). The relationship between MGS and age was examined using quantile regression analysis. Additionally, generalized linear model regression analysis was conducted to explore the influence of participants' demographics (gender, hand [L/R], hand length, hand circumference, age, weight, and height) on MGS. RESULTS: MGS measurements between raters showed excellent agreement (ICC(2,1) = 0.991, 95% confidence interval [0.98, 1.0]). The MGS and age relationship follows a curvilinear pattern, reaching a peak median MGS values of up to 20 kg between 30 and 49 years for females and up to 35 kg between 30 and 59 years for males. Subsequently, MGS declined as age advanced. Gender and hand (L/R) emerged as the primary factors influencing MGS, followed by hand length, hand circumference, age, weight, and height. CONCLUSIONS: The presented normative MGS reference values can be used for interpreting MGS measurements obtained from adults in the United Kingdom using GripAble. This study, along with previous studies on GripAble devices, confirms GripAble as a reliable and valid tool for measuring MGS.

Teaching, assessment and best practice in undergraduate psychiatry education in the UK: cross-sectional survey.

AIMS AND METHOD: We conducted a cross-sectional survey to examine how undergraduate psychiatry is taught and assessed across medical schools in the UK that have at least one cohort of graduated students. RESULTS: In total, 27 medical schools completed the survey. Curriculum coverage of common mental disorders, assessment skills and mental health law was broadly consistent, although exposure to psychiatric subspecialties varied. Significant variation existed regarding the duration of psychiatry placements and availability of enrichment activities. Small-group teaching, lectures and e-learning were the most frequent teaching modalities and various professionals and lived experience educators (patient and/or carers) contributed to teaching. Objective structured clinical examinations and multiple-choice questions dominated assessments. CLINICAL IMPLICATIONS: Medical schools should consider increasing students' exposure to different psychiatric subspecialties and integrating physical and mental health training to address comorbidity and promote holistic care. Future research should explore whether specific undergraduate experiences promote greater career interest and skills in psychiatry.

Chitosan functionalized doxorubicin loaded poly(methacrylamide) based copolymeric nanoparticles for enhanced cellular internalization and in vitro anticancer evaluation.

Doxorubicin (Dox), a chemotherapeutic agent, encounters challenges such as a short half-life, dose-dependent toxicity, and low solubility. In this context, the present study involved the fabrication of N-(2-hydroxypropyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) bearing P(HPMA-s-APMA) copolymeric nanoparticles (P(HPMA-s-APMA) NPs) and their investigation for efficient delivery of Dox. Furthermore, the synthesized nanoparticles (NPs) were coated with chitosan (Cht) to generate positively charged nanoformulations. The prepared formulations were evaluated for particle size, morphology, surface charge analysis, percentage encapsulation efficiency (EE%), and drug release studies. The anticancer activity of Cht-P(HPMA-s-APMA)-Dox NPs was assessed in the HeLa cancer cell line. The prepared P(HPMA-s-APMA)-Dox NPs exhibited an average particle size of 240-250 nm. Chitosan decorated P(HPMA-s-APMA)-Dox NPs displayed a significant increase in particle size, and the zeta potential shifted from negative to positive. The EE% for Cht-P(HPMA-s-APMA)-Dox NPs was calculated to be 68.06 %. The drug release studies revealed a rapid release of drug from Cht-P(HPMA-s-APMA)-Dox NPs at pH 4.8 than pH 7.4, demonstrating the pH-responsiveness of nanoformulation. Furthermore, the cell viability assay and internalization studies revealed that Cht-P(HPMA-s-APMA)-Dox NPs had a high cytotoxic response and significant cellular uptake. Hence, the Cht-P(HPMA-s-APMA)-Dox NPs appeared to be a suitable nanocarrier for effective, and safe chemotherapy.

Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent.

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.

Phosphorylation of AGO1a by MAP kinases is required for miRNA mediated resistance against Xanthomonas oryzae pv. oryzae infection in rice.

Bacterial leaf blight is a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo) which causes severe crop loss in rice. The molecular mechanism that initiates defense against such pathogens remains unexplored. Reports have suggested crucial role of several miRNAs in regulating immune responses in plants. Argonaute (AGO) proteins have been implicated in imparting immunity against pathogens by using small RNAs as guide molecules. Here, we show that phosphorylation of rice AGO1a by MAP kinases is required for miRNA expression regulation during Xoo infection. AGO1a is induced in response to pathogen infection and is under the control of SA signaling pathway. The pathogen responsive MAP kinases MPK3, MPK4 and MPK6, interact with AGO1a in planta and can phosphorylate the protein in vitro. Overexpression of AGO1a extends disease resistance against Xoo in rice and leads to a higher accumulation of miRNAs. Conversely, overexpression of a non phosphorylatable mutant protein aggravates disease susceptibility and remarkably suppresses the miRNA expression levels. At a molecular level, phosphorylation of AGO1a by MAP kinase is required for increased accumulation of miRNAs during pathogen challenge. Taken together, the data suggests that OsAGO1a is a direct phosphorylation target of MAP kinases and this phosphorylation is crucial for its role in imparting disease resistance.

Nano vs Resistant Tuberculosis: Taking the Lung Route.

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.

Public mental health through social media in the post COVID-19 era.

Social media is a powerful communication tool and a reflection of our digital environment. Social media acted as an augmenter and influencer during and after COVID-19. Many of the people sharing social media posts were not actually aware of their mental health status. This situation warrants to automate the detection of mental disorders. This paper presents a methodology for the detection of mental disorders using micro facial expressions. Micro-expressions are momentary, involuntary facial expressions that can be indicative of deeper feelings and mental states. Nevertheless, manually detecting and interpreting micro-expressions can be rather challenging. A deep learning HybridMicroNet model, based on convolution neural networks, is proposed for emotion recognition from micro-expressions. Further, a case study for the detection of mental health has been undertaken. The findings demonstrated that the proposed model achieved a high accuracy when attempting to diagnose mental health disorders based on micro-expressions. The attained accuracy on the CASME dataset was 99.08%, whereas the accuracy that was achieved on SAMM dataset was 97.62%. Based on these findings, deep learning may prove to be an effective method for diagnosing mental health conditions by analyzing micro-expressions.

A polyoxomolybdate-based hybrid nano capsule as an antineoplastic agent.

Polyoxometalates (POMs) are versatile anionic clusters which have attracted a lot of attention in biomedical investigations. To counteract the increasing resistance effect of cancer cells and the high toxicity of chemotherapeutic treatments, POM-based metallodrugs can be strategically synthesized by adjusting the stereochemical and physicochemical features of POMs. In the present report a polyoxomolybdate (POMo) based organic-inorganic hybrid solid (C6H16N)(C6H15N)2[Mo8O26]·3H2O, solid 1, has been synthesized and its antitumoral activities have been investigated against three cancer cell lines namely, A549 (Lung cancer), HepG2 (Liver cancer), and MCF-7 (Breast cancer) with IC50 values 56.2 µmol L-1, 57.3 µmol L-1, and 55.2 µmol L-1 respectively. The structural characterization revealed that solid 1 consists of an octa molybdate-type cluster connected by three triethylamine molecules via hydrogen bonding interactions. The electron microscopy analysis suggests the nanocapsule-like morphology of solid 1 in the size range of 50-70 nm. The UV-vis absorption spectra were used to assess the binding ability of synthesized POM-based solid 1 to calf thymus DNA (ctDNA), which further explained the binding interaction between POMo and ctDNA and the binding constant was calculated to be 2.246 × 103 giving evidence of groove binding.

Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity.

All nucleated cells express major histocompatibility complex I and interferon-γ (IFNγ) receptor1, but an epithelial cell-specific function of IFNγ signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNγ, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages. By contrast, antigen presentation by the tissue macrophages alongside inflammasome-associated interleukin-1α and interleukin-1ß production promotes a pathogenic transformation of CD4+ T cells into granulocyte-macrophage colony-stimulating-factor (GM-CSF)-producing T cells in vivo, which promotes colitis and colorectal cancer. Taken together, our study unravels critical checkpoints requiring IFNγ sensing and antigen presentation by epithelial cells that control the development of pathogenic CD4+ T cell responses in vivo.

Terahertz Spectroscopy of Aqueous Solutions of Sodium Halides (NaX): Self- and Cross-Correlation Contributions of Ions and Hydration Shell Water for X- = F-, Cl-, Br-, and I.

We investigated the terahertz (THz) absorption spectra of aqueous sodium halide solutions through molecular dynamics simulations using polarizable models of both water and ions. Specifically, we have considered aqueous solutions (∼1 M) of NaF, NaCl, NaBr, and NaI and calculated the difference THz spectrum of these solutions by subtracting the corresponding pure water contribution from the total THz spectrum of an ionic solution. The difference absorption spectrum of a given solution is then dissected into contributions from ion and ion-water correlations and also modifications of water-water correlations in the presence of the ions. The different components are further decomposed into induced dipole and permanent charge/dipole components and also into self- and cross-correlation components. The ion-water cross-correlation components are subsequently decomposed into contributions coming from different solvation shells through radially resolved calculations of such ion-water cross-correlations. Through all of these dissections, we could investigate the origin of different parts of the difference THz spectra of the sodium halide solutions studied here. It is found that while features below or around 100 cm-1 and also around 200 cm-1 arise mainly from ion and ion-water motion, that at the librational region above 600 cm-1 primarily originates from changes in water librational motion influenced by the ions. The variations of intensities of different components are also linked to the size and charge density of the anions in the solutions.

Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges.

The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24 to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a high-concern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24 to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks. GRAPHICAL ABSTRACT.