Microproteins/micropeptides dysregulation contributes to cancer progression and development: A mechanistic review.

Microproteins, known as micropeptides, are small protein molecules encoded by short open reading frames. These recently identified molecules have been proven to be an essential part of the human proteome that participates in multiple processes, such as DNA repair, mitochondrial respiration, and regulating different signaling pathways. A growing body of studies has evidenced that microproteins exhibit dysregulated expression levels in various malignancies and contribute to tumor progression. It has been reported that microproteins interact with many proteins, such as enzymes (e.g., adenosine triphosphate synthase) and signal transducers (e.g., c-Jun), and regulate malignant cell metabolism, proliferation, and metastasis. Moreover, microproteins have been found to play a significant role in multidrug resistance in vitro and in vivo by their activity in DNA repair pathways. Considering that, this review intended to summarize the roles of microproteins in different aspects of tumorigenesis with diagnostic and therapeutic perspectives.

Microscopic and molecular detection of piroplasms among sheep in Upper Egypt.

Introduction: Blood parasites pose a significant threat to livestock production in southern Egypt, yet there is a scarcity of information regarding their circulation and epidemiology in sheep in this region. This study aimed to investigate the seroprevalence of blood parasite infections in sheep in Assiut governorate, Upper Egypt. Methods: A total of 400 blood samples were collected from sheep of varying ages and genders. The preliminary screening for the presence of piroplasms, mainly Babesia and Theileria spp., via microscopic examination, followed by investigation of the potential risk factors linked with the exposure to infection. Moreover, molecular identification of both parasites on some of positive samples was performed using PCR targeting Babesia 18S rRNA and Theileria annulata Tams1 gene. Results: The microscopic examination revealed that among the examined sheep, there was an overall prevalence of blood parasites at 44% (176 out of 400), with Babesia spp. observed in 14% (56 out of 400) and Theileria spp. in 30% (120 out of 400). Furthermore, the infection rate was non-significantly higher in young animals (50%) compared to adults (38.5%) (P = 0.246). Male sheep exhibited a significantly higher vulnerability to both parasites' infection (63.3%) compared to females (35.7%) (P = 0.011). Interestingly, the prevalence of both blood parasites was significantly higher during the cold season (66.1%) compared to the hot season (15.9%) (P = < 0.001). The molecular analysis identified the presence of Babesia ovis and Theileria annulata among a subsample of the positive sheep's bloods films. The identified species were recorded in the GenBank™ databases and assigned specific accession numbers (OQ360720 and OQ360719 for B. ovis), and (OP991838 for T. annulata). Conclusions: Taken together, this study confirms a high prevalence of piroplasmosis and offers epidemiological and molecular insights into blood parasites in sheep from Upper Egypt, highlighting the importance of detecting these parasites in various hosts and their competent vectors (ticks).

Construction of multi-epitope vaccine against the Rhipicephalus microplus tick: an immunoinformatics approach.

Rhipicephalus microplus, known as the hard tick, is a vector for the parasites Babesia spp. and Anaplasma marginale, both of which can cause significant financial losses to the livestock industry. There is currently no effective vaccine for R. microplus tick infestations, despite the identification of numerous prospective tick vaccine candidates. As a result, the current research set out to develop an immunoinformatics-based strategy using existing methods for designing a multi-epitope based vaccination that is not only effective but also safe and capable of eliciting cellular and humoral immune responses. First, R. microplus proteins Bm86, Subolesin, and Bm95 were used to anticipate and link B and T-cell epitopes (HTL and CTL) to one another. Antigenicity testing, allergenicity assessment, and toxicity screening were just a few of the many immunoinformatics techniques used to identify potent epitopes. Multi-epitope vaccine design was chosen based on the antigenic score 0.935 that is promising vaccine candidate. Molecular docking was used to determine the nature of the interaction between TLR2 and the vaccine construct. Finally, molecular dynamic simulation was used to assess the stability and compactness of the resulting vaccination based on docking scores. The developed vaccine was shown to be stable, have immunogenic qualities, be soluble, and to have high expression by in silico cloning. These findings suggest that experimental investigation of the multi-epitope based vaccine designed in the current study will produce achievable vaccine candidates against R. microplus ticks, enabling more effective control of infestations.

Association between Serum Vitamin D Level and Acute Ischemic Stroke.

Stroke is one of the most common neurological disorder and third most common cause of death in the world. Low vitamin D concentrations have been shown to predict risk of cardiovascular disease and all-cause of mortality. The aim of this study was to estimate serum vitamin D level in acute ischemic stroke patients. This comparative cross-sectional type of study was conducted in the Department of Neurology and Department of Medicine at Mymensingh Medical College and Hospital, Bangladesh from November 2017 to June 2019 with a total number of 100 study subjects. Total fifty patients with acute ischemic stroke were enrolled in Group A and another fifty age and sex matched volunteer subjects were enrolled in Group B with no prior history of stroke or transient ischemic attacks. Serum vitamin D levels, fasting plasma glucose and lipid profile were assessed in both groups and compared with each other. P value <0.05 was considered as significant in the study. Mean fasting blood sugar, serum fasting total cholesterol (TC), serum fasting triglycerides, serum fasting Low density lipoprotein (LDL) were significantly higher in Group A than Group B (p<0.05). Serum vitamin D level in Group A was 25.28±8.47ng/ml and in Group B was 30.90±5.80, (p=0.001). Insufficient vitamin D level was found in 52.0% of ischemic stroke patients and in 30% of healthy controls (p=0.0002). Vitamin D deficiency was found in 20.0% ischemic stroke patients and 10.0% in healthy controls. This study demonstrates a positive association between low serum vitamin D level and acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.

Subclinical Hypothyroidism in Obese Children and Adolescents: Experience from Dhaka Shishu (Children) Hospital, Bangladesh.

Obesity and hypothyroidism are interlinked. In this prospective study, 142 children and adolescents (mean age 140±34 months, girls 54.2%) either with obesity or overweight were included from the patients attending at the Endocrine out-patient clinic of Dhaka Shishu (Children) Hospital during a period from March, 2017 to February, 2020 and were assessed for thyroid function. Among them, 85 were obese (Body mass index, BMI >95th percentile), 29 were overweight (BMI between 85th to 95th percentile) and 28 had normal weight (BMI <85th percentile). Girls were more frequent in obese (57.6%) and overweight (51.7%) groups than boys. Mean TSH was not significantly different among the three groups (3.39 vs. 4.01 vs. 4.06mIU/L; p=0.248). Subclinical hypothyroidism was present in 22 cases (15.5%); the frequencies were 3.6% in Group 1, 17.2% in Group 2 and 18.8% in Group 3. Both overweight and obese groups had significantly (p<0.005) higher prevalence of SCH than the normal-weight group. Girls were more frequently affected than boys (72.7% vs. 27.3%, p=0.047). Among the 22 children who had SCH, 2(9.1%) had a mild goiter and higher serum levels of anti-TPO and anti-TG. Serum TSH had no correlations with age, body weight, height, BMI and serum FT4. The findings indicate that a substantial portion of over weight and obese children and adolescents have SCH and the causes other than thyroid autoimmunity are more prevalent in them.

Structural studies of intrinsically disordered MLL-fusion protein AF9 in complex with peptidomimetic inhibitors.

AF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These proteins are two common MLL fusion partners in MLL-rearranged leukemias. The oncofusion proteins MLL-AF9/ENL recruit multiple binding partners, including the histone methyltransferase DOT1L, leading to aberrant transcriptional activation and enhancing the expression of a characteristic set of genes that drive leukemogenesis. The interaction between AF9 and DOT1L is mediated by an intrinsically disordered C-terminal ANC1 homology domain (AHD) in AF9, which undergoes folding upon binding of DOT1L and other partner proteins. We have recently reported peptidomimetics that disrupt the recruitment of DOT1L by AF9 and ENL, providing a proof-of-concept for targeting AHD and assessing its druggability. Intrinsically disordered proteins, such as AF9 AHD, are difficult to study and characterize experimentally on a structural level. In this study, we present a successful protein engineering strategy to facilitate structural investigation of the intrinsically disordered AF9 AHD domain in complex with peptidomimetic inhibitors by using maltose binding protein (MBP) as a crystallization chaperone connected with linkers of varying flexibility and length. The strategic incorporation of disulfide bonds provided diffraction-quality crystals of the two disulfide-bridged MBP-AF9 AHD fusion proteins in complex with the peptidomimetics. These successfully determined first series of 2.1-2.6 Å crystal complex structures provide high-resolution insights into the interactions between AHD and its inhibitors, shedding light on the role of AHD in recruiting various binding partner proteins. We show that the overall complex structures closely resemble the reported NMR structure of AF9 AHD/DOT1L with notable difference in the conformation of the ß-hairpin region, stabilized through conserved hydrogen bonds network. These first series of AF9 AHD/peptidomimetics complex structures are providing insights of the protein-inhibitor interactions and will facilitate further development of novel inhibitors targeting the AF9/ENL AHD domain.

Bio(sensors) based on molecularly imprinted polymers and silica materials used for food safety and biomedical analysis: Recent trends and future prospects.

In recent decades, analytical techniques have increasingly focused on the precise quantification. Achieving this goal has been accomplished with conventional analytical approaches that typically require extensive pretreatment methods, significant reagent usage, and expensive instruments. The need for rapid, simple, and highly selective identification platforms has become increasingly pronounced. Molecularly imprinted polymer (MIP) has emerged as a promising avenue for developing advanced sensors that can potentially surpass the limitations of conventional detection methods. In recent years, the application of MIP-silica materials-based sensors has garnered significant attention owing to their distinctive characteristics. These types of probes hold a distinct advantage in their remarkable stability and durability, all of which provide a suitable sensing platform in severe environments. Moreover, the substrate composed of silica materials offers a vast surface area for binding, thereby facilitating the efficient detection of even minuscule concentrations of targets. As a result, sensors based on MIP-silica materials have the potential to be widely applied in various industries, including medical diagnosis, and food safety. In the present review, we have conducted an in-depth analysis of the latest research developments in the field of MIPs-silica materials based sensors, with a focus on succinctly summarizing and elucidating the most crucial findings. This is the first comprehensive review of integration MIPs with silica materials in electrochemical (EC) and optical probes for biomedical analysis and food safety.

Expression of concern: Palladium supported on mixed-metal-organic framework (Co-Mn-MOF-74) for efficient catalytic oxidation of CO.

Expression of Concern for 'Palladium supported on mixed-metal-organic framework (Co-Mn-MOF-74) for efficient catalytic oxidation of CO' by Reda S. Salama et al., RSC Adv., 2021, 11, 4318-4326, https://doi.org/10.1039/D0RA09970H.

Elucidating the role of EPPK1 in lung adenocarcinoma development.

BACKGROUND: We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development. METHODS: EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically. RESULTS: EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO. CONCLUSIONS: Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.

Self-micellizing solid dispersion of thymoquinone with enhanced biopharmaceutical and nephroprotective effects.

The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was selected as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5-15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.

ß-Cell Insulin Resistance Plays a Causal Role in Fat-Induced ß-Cell Dysfunction In Vitro and In Vivo.

In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in ß-cells where they play a role in ß-cell function. Therefore, inhibition of the insulin/insulin-like growth factor 1 pathway may be involved in fat-induced ß-cell dysfunction. To address the role of ß-cell insulin resistance in FFA-induced ß-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 hours in rats. BPV, a tyrosine phosphatase inhibitor, acts as an insulin mimetic and is devoid of any antioxidant effect that could prevent ß-cell dysfunction, unlike most insulin sensitizers. Following fat infusion, rats either underwent hyperglycemic clamps for assessment of ß-cell function in vivo or islets were isolated for ex vivo assessment of glucose-stimulated insulin secretion (GSIS). We also incubated islets with oleate or palmitate and BPV for in vitro assessment of GSIS and Akt (protein kinase B) phosphorylation. Next, mice with ß-cell specific deletion of PTEN (phosphatase and tensin homolog; negative regulator of insulin signaling) and littermate controls were infused with oleate for 48 hours, followed by hyperglycemic clamps or ex vivo evaluation of GSIS. In rat experiments, BPV protected against fat-induced impairment of ß-cell function in vivo, ex vivo, and in vitro. In mice, ß-cell specific deletion of PTEN protected against oleate-induced ß-cell dysfunction in vivo and ex vivo. These data support the hypothesis that ß-cell insulin resistance plays a causal role in FFA-induced ß-cell dysfunction.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

Successful treatment of recurrent visceral leishmaniasis relapse in an immunocompetent adult female with functional hypopituitarism in Bangladesh.

BACKGROUND: Currently available treatment options are mostly effective in achieving long-term cure in visceral leishmaniasis (VL) patients. However, there have been reports of recurrence of this illness in both immunosuppressed and immunocompetent patients. CASE PRESENTATION: We report the first case of recurrent VL relapse in a 19-year-old immunocompetent female with functional hypopituitarism (hypogonadotropic hypogonadism with central hypothyroidism) from Bangladesh, who has been treated three times previously with optimal dosage and duration- liposomal amphotericin B (LAmB) alone and in combination with miltefosine. We treated the patient successfully with a modified treatment regimen of 10 mg/kg body weight LAmB for two consecutive days along with oral miltefosine for seven days as loading dose. For secondary prophylaxis, the patient received 3 mg/kg body weight LAmB along with oral miltefosine for seven days monthly for five doses followed by hormonal replacement. The patient remained relapse free after 12 months of her treatment completion. CONCLUSION: In the absence of protective vaccines against Leishmania species and standard treatment regimen, this modified treatment regimen could help the management of recurrent relapse cases.

Parkinson's Disease and MicroRNAs: A Duel Between Inhibition and Stimulation of Apoptosis in Neuronal Cells.

Parkinson's disease (PD) is one of the most prevalent diseases of central nervous system that is caused by degeneration of the substantia nigra's dopamine-producing neurons through apoptosis. Apoptosis is regulated by initiators' and executioners' caspases both in intrinsic and extrinsic pathways, further resulting in neuronal damage. In that context, targeting apoptosis appears as a promising therapeutic approach for treating neurodegenerative diseases. Non-coding RNAs-more especially, microRNAs, or miRNAs-are a promising target for the therapy of neurodegenerative diseases because they are essential for a number of cellular processes, including signaling, apoptosis, cell proliferation, and gene regulation. It is estimated that a substantial portion of coding genes (more than 60%) are regulated by miRNAs. These small regulatory molecules can have wide-reaching consequences on cellular processes like apoptosis, both in terms of intrinsic and extrinsic pathways. Furthermore, it was recommended that a disruption in miRNA expression levels could also result in perturbation of typical apoptosis pathways, which may be a factor in certain diseases like PD. The latest research on miRNAs and their impact on neural cell injury in PD models by regulating the apoptosis pathway is summarized in this review article. Furthermore, the importance of lncRNA/circRNA-miRNA-mRNA network for regulating apoptosis pathways in PD models and treatment is explored. These results can be utilized for developing new strategies in PD treatment.

Recent advances in natural nanoclay for diagnosis and therapy of cancer: A review.

Cancer is still one of the deadliest diseases, and diagnosing and treating it effectively remains difficult. As a result, advancements in earlier detection and better therapies are urgently needed. Conventional chemotherapy induces chemoresistance, has non-specific toxicity, and has a meager efficacy. Natural materials like nanosized clay mineral formations of various shapes (platy, tubular, spherical, and fibrous) with tunable physicochemical, morphological, and structural features serve as potential templates for these. As multifunctional biocompatible nanocarriers with numerous applications in cancer research, diagnosis, and therapy, their submicron size, individual morphology, high specific surface area, enhanced adsorption ability, cation exchange capacity, and multilayered organization of 0.7-1 nm thick single sheets have attracted significant interest. Kaolinite, halloysite, montmorillonite, laponite, bentonite, sepiolite, palygorskite, and allophane are the most typical nanoclay minerals explored for cancer. These multilayered minerals can function as nanocarriers to effectively carry a variety of anticancer medications to the tumor site and improve their stability, dispersibility, sustained release, and transport. Proteins and DNA/RNA can be transported using nanoclays with positive and negative surfaces. The platform for phototherapeutic agents can be nanoclays. Clays with bio-functionality have been developed using various surface engineering techniques, which could help treat cancer. The promise of nanoclays as distinctive crystalline materials with applications in cancer research, diagnostics, and therapy are examined in this review.

Xpert MTB/RIF Ultra for the rapid diagnosis of extrapulmonary tuberculosis in a clinical setting of high tuberculosis prevalence country and interpretation of 'trace' results.

To evaluate the diagnostic performance of Xpert MTB/RIF Ultra (Ultra) for the diagnosis of extrapulmonary tuberculosis (EPTB) from different types of extrapulmonary specimens in comparison with culture and composite microbiological reference standard (CRS). A total of 240 specimens were prospectively collected from presumptive EPTB patients between July 2021-January 2022 and tested by Ultra, Xpert, culture and acid-fast bacilli (AFB) smear microscopy. Out of 240 specimens, 35.8 %, 20.8 %, 11.3 %, and 7.1 % were detected as Mycobacterium tuberculosis complex by Ultra, Xpert, culture and AFB microscopy, respectively. An additional 15.0 % cases were detected by Ultra compared to Xpert MTB/RIF (Xpert) assay. A total of 28 (11.7 %) cases were identified as 'trace' category by Ultra with indeterminate rifampicin resistance result; of which 36.4 % were clinically confirmed as EPTB. Compared to culture, the sensitivity and specificity of Ultra and Xpert were 100 % and 72.3 %; 92.6 % and 88.3 %, respectively. In comparison with CRS, these were respectively: 98.9 % and 100 %; 57.5 % and 100 %. For individual category of specimens, sensitivity of Ultra was 100 % with varying specificity. We found that Ultra was highly sensitive for the rapid diagnosis of EPTB and has extensive potential over current diagnostics in high TB burden countries, but 'trace' results should be interpreted with caution.

COX 2-inhibitors; a thorough and updated survey into combinational therapies in cancers.

Cyclooxygenase (COX) enzymes are pivotal in inflammation and cancer development. COX-2, in particular, has been implicated in tumor growth, angiogenesis, and immune evasion. Recently, COX-2 inhibitors have arisen as potential therapeutic agents in cancer treatment. In addition, combining COX inhibitors with other treatment modalities has demonstrated the potential to improve therapeutic efficacy. This review aims to investigate the effects of COX inhibition, both alone and in combination with other methods, on signaling pathways and carcinogenesis in various cancers. In this study, a literature search of all major academic databases was conducted (PubMed, Scholar google), including the leading research on the mechanisms of COX-2, COX-2 inhibitors, monotherapy with COX-2 inhibitors, and combining COX-2-inhibitors with chemotherapeutic agents in tumors. The study encompasses preclinical and clinical evidence, highlighting the positive findings and the potential implications for clinical practice. According to preclinical studies, multiple signaling pathways implicated in tumor cell proliferation, survival, invasion, and metastasis can be suppressed by inhibiting COX. In addition, combining COX inhibitors with chemotherapy drugs, targeted therapies, immunotherapies, and miRNA-based approaches has enhanced anti-tumor activity. These results suggest that combination therapy has the potential to overcome resistance mechanisms and improve treatment outcomes. However, caution must be exercised when selecting and administering combination regimens. Not all combinations of COX-2 inhibitors with other drugs result in synergistic effects; some may even have unfavorable interactions. Therefore, personalized approaches that consider the specific characteristics of the cancer and the medications involved are crucial for optimizing therapeutic strategies. In conclusion, as monotherapy or combined with other methods, COX inhibition bears promise in modulating signaling pathways and inhibiting carcinogenesis in various cancers. Additional studies and well-designed clinical trials are required to completely elucidate the efficacy of COX inhibition and combination therapy in enhancing cancer treatment outcomes. This narrative review study provides a detailed summary of COX-2 monotherapy and combination targeted therapy in cancer treatment.

Endoscopic Transnasal Repair of Cerebrospinal Fluid Leakage: Experience in BSMMU.

Endoscopic transnasal repair of CSF rhinorrhoea is gaining popularity around the world because of its tremendous success rate but it depends on defect site, size, technique of repair, experiences of surgeon and also patient's profile. Aim of this study was to analysis of surgical outcome of endoscopic transnasal repair of CSF rhinorrhoea. A retrospective study carried out in the department of ENT and Head neck surgery at Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2018 to December 2019. Of the total of 24 patients 16(66.0%) were female and 8(33.0%) males. The commonest site of the leak was in the cribriform plate in 18(75.3%) followed by 5(20.8%) in the fovea ethmoidalis, and 1(4.0%) in the sphenoid sinus, the overall success rate of this series with first surgical procedure was 95.83% and 100.0% with a second procedure. Meticulous pre-operative evaluation, proper identification of leakage site, choice of graft materials and surgical technique are keys to attaining excellent results.

Spermidine constitutes a key determinant of motility and attachment of Salmonella Typhimurium through a novel regulatory mechanism.

Spermidine is a poly-cationic molecule belonging to the family of polyamines and is ubiquitously present in all organisms. Salmonella synthesizes, and harbours specialized transporters to import spermidine. A group of polyamines have been shown to assist in Salmonella Typhimurium's virulence and regulation of Salmonella pathogenicity Inslad 1 (SPI-1) genes and stress resistance; however, the mechanism remains elusive. The virulence trait of Salmonella depends on its ability to employ multiple surface structures to attach and adhere to the surface of the target cells before invasion and colonization of the host niche. Our study discovers the mechanism by which spermidine assists in the early stages of Salmonella pathogenesis. For the first time, we report that Salmonella Typhimurium regulates spermidine transport and biosynthesis processes in a mutually inclusive manner. Using a mouse model, we show that spermidine is critical for invasion into the murine Peyer's patches, which further validated our in vitro cell line observation. We show that spermidine controls the mRNA expression of fimbrial (fimA) and non-fimbrial adhesins (siiE, pagN) in Salmonella and thereby assists in attachment to host cell surfaces. Spermidine also regulated the motility through the expression of flagellin genes by enhancing the translation of sigma-28, which features an unusual start codon and a poor Shine-Dalgarno sequence. Besides regulating the formation of the adhesive structures, spermidine tunes the expression of the two-component system BarA/SirA to regulate SPI-1 encoded genes. Thus, our study unravels a novel regulatory mechanism by which spermidine exerts critical functions during Salmonella Typhimurium pathogenesis.

Fine-Root Distribution and Soil Physicochemical Property Variations in Four Contrasting Urban Land-Use Types in South Korea.

Urbanization and associated forest conversions have given rise to a continuum of native (forest fragments) and modified (artificial grasslands and perennial ecosystems) land-use types. However, little is known about how these shifts affect soil and fine-root compartments that are critical to a functioning carbon and nutrient circulation system. In this study, soil physicochemical properties, fine-root mass, and vertical distribution patterns were investigated in four representative urban land-use types: grassland (ZJ), perennial agroecosystem (MP), broadleaf deciduous forest patch (QA), and coniferous evergreen forest patch (PD). We quantified the fine-root mass in the upper 30 cm vertical profile (0-30 cm) and at every 5 cm depth across three diameter classes (<2 mm, 2-5 mm, and <5 mm). Soil physicochemical properties, except for phosphorus, nitrogen, ammonium nitrogen, and sodium cations, varied significantly across land-use types. The total root biomass (<5 mm) decreased in the order of QA (700.3 g m-2) > PD (487.2 g m-2) > ZJ (440.1 g m-2) > MP (98.3 g m-2). The fine-root mass of ZJ and MP was correlated with soil nutrients, which was attributed to intensive management operations, while the fine-root mass of QA and PD had a significant relationship with soil organic matter due to the high inputs from forest litter. Very fine roots (<2 mm) presented a distinct decremental pattern with depth for all land-use types, except for MP. Very fine roots populated the topmost 5 cm layer in ZJ, QA, and PD at 52.1%, 49.4%, and 39.4%, respectively. Maintaining a woody fine-root system benefits urban landscapes by promoting soil stabilization, improving ground infiltration rates, and increasing carbon sequestration capacity. Our findings underscore the importance of profiling fine-root mass when assessing urban expansion effects on terrestrial ecosystems.