The oral microbiome of newly diagnosed tuberculosis patients; a pilot study.

BACKGROUND: Changes in oral microbiota composition (dysbiosis) have long been known to play a key role in the pathogenesis of oral and systemic diseases including respiratory diseases. However, till now, no study has assessed changes in oral microbiota following tuberculosis (TB) infection in humans. AIMS: This is the first study of its kind that aimed to investigate oral microbial dysbiosis in newly diagnosed, treatment naïve, TB patients. METHODS: Oral swab samples were collected from newly diagnosed TB patients (n = 20) and age, gender and ethnicity matched healthy controls (n = 10). DNA was extracted and microbiota analyzed by sequencing the hypervariable (V3-V4) region of the bacterial 16S rRNA gene using Illumina MiSeq platform. Bioinformatics and statistical analyses were performed using QIIME and R. RESULTS: Bacterial richness, diversity and community composition were significantly different between TB patients and healthy controls. The two groups also exhibit differential abundance at phylum, class, genus and species levels. LEfSe analysis revealed enrichment (LDA scores (log10) >2, P < 0.05) of Firmicutes (especially Streptococcus) and Actinobacteriota (especially Rothia) in TB patients relative to healthy controls. Gene function prediction analysis showed upregulation of metabolic pathways related to carbohydrates (butanoate, galactose) and fatty acids metabolism, antibiotics biosynthesis, proteosome and immune system signaling. CONCLUSION: These observations suggest significant variations in diversity, relative abundance and functional potential of oral microbiota of TB patients compared to healthy controls thereby suggesting potential role of oral bacterial dysbiosis in TB pathogenesis. However, longitudinal studies using powerful metagenomic and transcriptomic approaches are crucial to more fully understand and confrim these findings.

Low Temperature Synthesis of 2D p-Type α-In2 Te3 with Fast and Broadband Photodetection.

2D A 2 III B 3 VI ${\mathrm{A}}_2^{{\mathrm{III}}}{\mathrm{B}}_3^{{\mathrm{VI}}}$ compounds (A = Al, Ga, In, and B = S, Se, and Te) with intrinsic structural defects offer significant opportunities for high-performance and functional devices. However, obtaining 2D atomic-thin nanoplates with non-layered structure on SiO2 /Si substrate at low temperatures is rare, which hinders the study of their properties and applications at atomic-thin thickness limits. In this study, the synthesis of ultrathin, non-layered α-In2 Te3  nanoplates is demonstrated using a BiOCl-assisted chemical vapor deposition method at a temperature below 350 °C on SiO2 /Si substrate. Comprehensive characterization results confirm the high-quality single crystal is the low-temperature cubic phase α-In2 Te3 , possessing a noncentrosymmetric defected ZnS structure with good second harmonic generation. Moreover, α-In2 Te3 is revealed to be a p-type semiconductor with a direct and narrow bandgap value of 0.76 eV. The field effect transistor exhibits a high mobility of 18 cm2 V-1  s-1 , and the photodetector demonstrates stable photoswitching behavior within a broadband photoresponse from 405 to 1064 nm, with a satisfactory response time of τrise = 1 ms. Notably, the α-In2 Te3 nanoplates exhibit good stability against ambient environments. Together, these findings establish α-In2 Te3 nanoplates as promising candidates for next-generation high-performance photonics and electronics.

Coherent control of photonic band gaps through the relative phase using modified superradiance lattice.

We report photonic band gaps based on a modified superradiance lattice having reflectivity close to 100% for both the low and high-frequency ranges. We observe that tuning the relative phase between the coupling fields provides additional control over photonic band gaps. We notice that the relative phase can control three input channels of the probe field simultaneously and efficiently. This feature of relative phase over photonic band gaps provides potential in the field of quantum optics. Further, this scheme is experimentally more viable. Rubidium atoms 87Rb can obtain low-frequency (infrared) photonic band gaps. On the other hand, rubidium atoms 85Rb and beryllium ions Be2+ can form high-frequency ultraviolet and soft X-ray photonic band gaps, achieving reflectivities of 80% and 96%, respectively. This scheme holds promise for constructing highly efficient optical switches and beam splitters.

Spectrum of initial clinical presentations in Pakistani patients with systemic lupus erythematosus in the Arthritis Care Foundation lupus cohort.

OBJECTIVE: The aim is to determine the pattern of initial clinical presentations of systemic lupus erythematous (SLE) in patients in a Pakistani lupus cohort. METHODS: This is a multi-centric, retrospective, descriptive study that was done through the analysis of electronic records of patients registered with outdoor clinics of the Arthritis Care Foundation (ACF) from November 2021 to March 2023. Follow-up records of all patients diagnosed and labeled as SLE as per ACR/EULAR criteria 2019 were reviewed and only those patients whose initial presentation of SLE was documented at their incident visit (after verifying the signs and symptoms from record of their GP/referring physicians' visits) were included in the study. A total of 388 patients diagnosed with SLE were included in the study. Their data was then entered and analyzed by using SPSS 23. The qualitative data was expressed as percentages and numbers while the quantitative variables were expressed as mean and standard deviation. Data correlation was calculated by Chi-Square test, and a p-value of less than 0.05 was considered statistically significant. RESULTS: Of our 388 patients, 360 (92.8%) were females and 28 (7.2%) were males giving a female-to-male ratio of 12:1. The mean age of our patients was 32.8 + 9.8 years. Mucocutaneous manifestations were most commonly reported in our patient group by 336 (86.7%) patients. Musculoskeletal complaints were the next most common presenting feature reported by 246 (61.9%) patients followed by constitutional symptoms in 78 (20.1%) patients, and renal involvement in 42 (10.8%) patients. CONCLUSION: In our study, a majority of patients presented with mucocutaneous symptoms. It is therefore of paramount importance to suspect autoimmune diseases in patients with these system involvements.

Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions.

The recruitment of cells with effector functions into the tumor microenvironment holds potential for delaying cancer progression. We show that subsets of human CD28-effector CD8 T cells, CCR7- CD45RO+ effector memory, and CCR7- CD45RO- effector memory RA phenotypes, express the chemerin receptor CMKLR1 and bind chemerin via the receptor. CMKLR1-expressing human CD8 effector memory T cells present gene, protein, and cytotoxic features of NK cells. Active chemerin promotes chemotaxis of CMKLR1-expressing CD8 effector memory cells and triggers activation of the α4ß1 integrin. In an experimental prostate tumor mouse model, chemerin expression is downregulated in the tumor microenvironment, which is associated with few tumor-infiltrating CD8+ T cells, while forced overexpression of chemerin by mouse prostate cancer cells leads to an accumulation of intra-tumor CD8+ T cells. Furthermore, α4 integrin blockade abrogated the chemerin-dependent recruitment of CD8+ T effector memory cells into implanted prostate tumors in vivo. The results identify a role for chemerin:CMKLR1 in defining a specialized NK-like CD8 T cell, and suggest the use of chemerin-dependent modalities to target effector CMKLR1-expressing T cells to the tumor microenvironment for immunotherapeutic purposes.

Physicochemical Evaluation and Pharmacological Screening of Fernando Adenophylla Steenis Fruits.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200mg/kg extract dose exhibited %age pain inhibition of 55.12% and reduced body temperature from 39.78±0.03°C to 37.22±0.02°C in hyperthermic rats. A decrease in blood glucose levels up to 57.88% was observed on the 21st day of the treatment with 500mg/kg ethanolic extract.

Quality and antioxidant potential of goat's milk paneer prepared from different citrus juices and its whey.

The experiments reported in this research paper aimed to evaluate the physico-chemical and sensory characteristics, microbial quality and antioxidant potential of goat's milk paneer during storage (0-12 d, 4 ± 1°C). The juices from five different citrus fruits were used as coagulant (treatments) to make goat's milk paneer. The pH of all paneer samples decreased during storage whereas titratable acidity increased. Ash (%) fat (%) and protein (%) of paneer increased slightly during storage, whereas sensory perception decreased. The juices from all the citrus fruit varieties showed high contents of total phenolics and total flavonoids which ultimately influenced ferric reducing antioxidant power, total antioxidant capacity and radical scavenging activities. As the contents of different juices were also retained in the paneer matrix, so paneer coagulated with citrus juices also showed encouraging results in terms of total phenolic and flavonoid contents, ferric reducing antioxidant power and radical scavenging activities. Amongst all the paneers, the most promising was that coagulated by kinnow juice. In addition, the whey obtained from paneer coagulated by citrus juices also showed appreciable quantities of total phenolic and flavonoid contents, thereby beneficially influencing ferric reducing antioxidant power andradical scavenging activities. It is concluded that citrus juices improve the sensorial quality and antioxidant potential of goat's milk paneer and its whey.

Analyzing the impact of pesticides on the indus river: contamination levels in water, sediment, fish, and associated human health risks.

Pesticides are frequently used to protect crop yields and manage malaria vectors; however, their inadvertent transport into aquatic habitats poses a significant concern. Various anthropogenic activities influence the Indus River in Pakistan. This study aimed to assess the presence of eight pesticide residues at three different sites (Kalabagh, Kundian, and Chashma) in water, sediment, and the fish species (Labeo rohita) during both dry and wet seasons to measure the intensity of this pressure. Pesticide analysis was carried out using gas chromatography equipped with an electron capture detector. The results revealed the highest concentrations of pesticides during both dry and wet seasons at all sites, measuring 0.83 and 0.62 µg/l (water), 12.37 and 9.20 µg/g/dw (sediment), and 14.27 and 11.29 µg/g/ww (L. rohita), respectively. Overall, pesticide concentrations were higher in the dry season than in the wet season across all study sites. Based on detection frequency and concentration in both seasons at all sites, dominant pesticides included cypermethrin and carbofuran (in water), as well as endosulfan and cypermethrin (in sediment and fish tissue). Levels of endosulfan and cypermethrin exceeded standard limits. Moreover, principal component analysis (PCA) indicated no correlation among pesticides in fish tissue, sediment, and water. However, pesticides exhibited different behavior in different seasons. Furthermore, endosulfan and triazophos impose great human health risk, as indicated by the THQ value (> 1). The overall HI value was greater for site 1 in the dry season (8.378). The study concluded that the presence of agricultural pesticides in the Indus River poses a risk to aquatic life and has the potential to disrupt the entire food chain. This highlights the importance of sustainable practices for the study area and Pakistan overall agricultural and environmental sustainability. It is further recommended to strengthen regulations for reduced pesticide use and promote eco-friendly pest management.

Bacillus subtilis: current and future modification strategies as a protein secreting factory.

Bacillus subtilis is regarded as a promising microbial expression system in bioengineering due to its high stress resistance, nontoxic, low codon preference and grow fast. The strain has a relatively efficient expression system, as it has at least three protein secretion pathways and abundant molecular chaperones, which guarantee its expression ability and compatibility. Currently, many proteins are expressed in Bacillus subtilis, and their application prospects are broad. Although Bacillus subtilis has great advantages compared with other prokaryotes related to protein expression and secretion, it still faces deficiencies, such as low wild-type expression, low product activity, and easy gene loss, which limit its large-scale application. Over the years, many researchers have achieved abundant results in the modification of Bacillus subtilis expression systems, especially the optimization of promoters, expression vectors, signal peptides, transport pathways and molecular chaperones. An optimal vector with a suitable promoter strength and other regulatory elements could increase protein synthesis and secretion, increasing industrial profits. This review highlights the research status of optimization strategies related to the expression system of Bacillus subtilis. Moreover, research progress on its application as a food-grade expression system is also presented, along with some future modification and application directions.

Mycophenolate mofetil vs. cyclophosphamide-based induction regimens for lupus nephritis: Outcomes at a tertiary care centre in Lahore, Pakistan.

Objectives: To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. METHODS: The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26. RESULTS: Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05). CONCLUSIONS: Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.

Renal histaminergic system and acute effects of histamine receptor 2 blockade on renal damage in the Dahl salt-sensitive rat.

Histamine is involved in the regulation of immune response, vasodilation, neurotransmission, and gastric acid secretion. Although elevated histamine levels and increased expression of histamine metabolizing enzymes have been reported in renal disease, there is a gap in knowledge regarding the mechanisms of histamine-related pathways in the kidney. We report here that all four histamine receptors as well as enzymes responsible for the metabolism of histamine are expressed in human and rat kidney tissues. In this study, we hypothesized that the histaminergic system plays a role in salt-induced kidney damage in the Dahl salt-sensitive (DSS) rat, a model characterized with inflammation-driven renal lesions. To induce renal damage related to salt sensitivity, DSS rats were challenged with 21 days of a high-salt diet (4% NaCl); normal-salt diet (0.4% NaCl)-fed rats were used as a control. We observed lower histamine decarboxylase and higher histamine N-methyltransferase levels in high-salt diet-fed rats, indicative of a shift in histaminergic tone; metabolomics showed higher histamine and histidine levels in the kidneys of high-salt diet-fed rats, whereas plasma levels for both compounds were lower. Acute systemic inhibition of histamine receptor 2 in the DSS rat revealed that it lowered vasopressin receptor 2 in the kidney. In summary, we established here the existence of the local histaminergic system, revealed a shift in the renal histamine balance during salt-induced kidney damage, and provided evidence that blockage of histamine receptor 2 in the DSS rat affects water balance and urine concentrating mechanisms.NEW & NOTEWORTHY Histamine is a nitrogenous compound crucial for the inflammatory response. The knowledge regarding the renal effects of histamine is very limited. We showed that renal epithelia exhibit expression of the components of the histaminergic system. Furthermore, we revealed that there was a shift in the histaminergic tone in salt-sensitive rats when they were challenged with a high-salt diet. These data support the notion that histamine plays a role in renal epithelial physiological and pathophysiological functions.

Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

The Independent Effects of Kidney Length and Vascular Plaque on Ten-Year Outcomes of Extended Criteria Donor Kidney Transplants.

The independent effects of deceased donor kidney length and vascular plaque on long-term graft survival are not established. Utilizing DonorNet attachments from 4,480 expanded criteria donors (ECD) recovered between 2008 and 2012 in the United States with at least one kidney biopsied and transplanted, we analyzed the relationship between kidney length and vascular plaques and 10-year hazard of all-cause graft failure (ACGF) using causal inference methods in a Cox regression framework. The composite plaque score (range 0-4) and the presence of any plaque (yes, no) was also analyzed. Kidney length was modeled both categorically (<10, 10-12, >12 cm) as well as numerically, using a restricted cubic spline to capture nonlinearity. Effects of a novel composite plaque score 4 vs. 0 (HR 1.08; 95% CI: 0.96, 1.23) and the presence of any vascular plaque (HR 1.08; 95% CI: 0.98, 1.20) were attenuated after adjustment. Likewise, we identified a potential nonlinear relationship between kidney length and the 10-year hazard of ACGF, however the strength of the relationship was attenuated after adjusting for other donor factors. The independent effects of vascular plaque and kidney length on long-term ECD graft survival were found to be minimal and should not play a significant role in utilization.

Exploring chromone sulfonamides and sulfonylhydrazones as highly selective ectonucleotidase inhibitors: Synthesis, biological evaluation and in silico study.

Ectonucleotidases, a well-known superfamily of plasma membrane located metalloenzymes plays a central role in mediating the process of purinergic cell signaling. Major functions performed by these enzymes include the hydrolysis of extracellular nucleosides and nucleotides which are considered as important cell-signaling molecules. Any (patho)-physiologically induced disruption in this purinergic cell signaling leads to several disorders, hence these enzymes are important drug targets for therapeutic purposes. Among the major challenges faced in the design of inhibitors of ectonucleotidases, an important one is the lack of selective inhibitors. Access to highly selective inhibitors via a facile synthetic route will not only be beneficial therapeutically, but will also lead to an increase in our understanding of intricate interplay between members of ectonucleotidase enzymes in relation to their selective activation and/or inhibition in different cells and tissues. Herein we describe synthesis of highly selective inhibitors of human intestinal alkaline phosphatase (h-IAP) and human tissue non-specific alkaline phosphatase (h-TNAP), containing chromone sulfonamide and sulfonylhydrazone scaffolds. Compound 1c exhibited highest (and most selective) h-IAP inhibition activity (h-IAP IC50 = 0.51 ± 0.20 µM; h-TNAP = 36.5%) and compound 3k showed highest activity and selective inhibition against h-TNAP (h-TNAP IC50 = 1.41 ± 0.10 µM; h-IAP = 43.1%). These compounds were also evaluated against another member of ectonucleotidase family, that is rat and human ecto-5'-nucleotidase (r-e5'NT and h-e5'NT). Some of the compounds exhibited excellent inhibitory activity against ecto-5'-nucleotidase. Compound 2 g exhibited highest inhibition against h-e5'NT (IC50 = 0.18 ± 0.02 µM). To rationalize the interactions with the binding site, molecular docking studies were carried out.

Sugarcane-bagasse-ash in enhanced mesophilic Co-digestion for biogas and nutrient recovery: A concept of developing rural circular bioeconomy.

Conductive agro-industrial wastes as accelerants in the anaerobic digestion (AD) of organic waste is a good technique for developing a rural circular economy, such as producing bioenergy and biofertilizer. This study disclosed the a role of sugar cane bagasse ash (SCBA) in enhancing the bioenergy (biogas) yield and digestate fertility via anaerobic co-digestion (AcoD) of buffalo dung (BD) and vegetable residue (VR) under mesophilic conditions (37 á´¼C). Firstly, an optimal BD/VR ratio (1:3) was determined based on biogas yield by introducing five different BD/VR ratios (1:0, 3:1, 1:1, 1:3, and 0:1) into AcoD systems. Secondly, the biogas yield was increased further by adding SCBA at five different concentrations (0, 0.5, 1, 1.5, and 2 wt%). Experimental results disclosed that the 1.5 wt% of SCBA gave the highest cumulative biogas yield (153.67 mL/g VS), COD removal rate (31.18%), and fertility (5.08%). Moreover, a framework is suggested to understand the role of SCBA in the enhanced DIET mechanism. This work documents an environmentally friendly and economical technique for developing a rural circular bioeconomy via the AD of organic agro-waste.

Role of Yeast and Yeast-Derived Products as Feed Additives in Broiler Nutrition.

Antibiotic resistance is looming problem in broiler production globally and there has been an increasing interest to look for sustainable alternatives to antibiotics. Yeast and its derived products are recognized as potential feed additives because of their beneficial impacts on poultry. Particularly, yeast exhibited positive effects on the humoral immunity by increasing serum immunoglobulin (Ig) A levels. Moreover, yeast and its products showed immune adjuvant-like properties that helped the broilers chicken to develop faster and stronger innate immune response under pathogenic challenges. Use of yeast and its products as prebiotic/probiotic improves the gut architecture mainly by improving the gut development and gut microbiome, reduction in colonization of pathogens through competitive exclusion, binding of toxins and enhancing digestion and absorption of nutrients. These unique properties of yeast and yeast products enhance animal welfare and productivity; warrant them to be used as a promising feed additive. This article, therefore, provides insights into the functional role of yeast and its products in the broiler diets and highlights its importance as a commercially viable alternative of synthetic antibiotic growth promoters in the broiler feed industry.

Phytosterol: nutritional significance, health benefits, and its uses in poultry and livestock nutrition.

Medicinal plants with active ingredients have shown great potential as natural and sustainable additives in livestock and poultry diets as growth promoters, performance, feed conversion ratio, digestibility of nutrient enhancers, and antioxidants and immune system modulators. Among active ingredients, phytosterols, which are plant-based bio-factors that may be found in seeds, fruits, grains, vegetables and legumes, are thought to be involved in the aforementioned activities but are also widely known in human medicine due to their efficacy in treating diabetes, coronary heart disease, and tumors. Nevertheless, phytosterols can also promote carcinogens production, angiogenesis inhibition, metastasis, infiltration, and cancer cells proliferation. This review focuses on the deepening of the biological role and health benefits of phytosterols and their new potential application in poultry and livestock nutrition.

Plant growth promoting rhizobacteria induced metal and salt stress tolerance in Brassica juncea through ion homeostasis.

Soil heavy metal contamination and salinity constitute a major environmental problem worldwide. The affected area and impact of these problems are increasing day by day; therefore, it is imperative to restore their potential using environmentally friendly technology. Plant growth-promoting rhizobacteria (PGPR) provides a better option in this context. Thirty-seven bacteria were isolated from the rhizosphere of maize cultivated in metal- and salt-affected soils. Some selected bacterial strains grew well under a wide range of pH (4-10), salt (5-50 g/L), and Cd (50-1000 mg/L) stress. Three bacterial strains, Exiguobacterium aestuarii (UM1), Bacillus cereus (UM8), and Bacillus megaterium (UM35), were selected because of their robust growth and high tolerance to both stress conditions. The bacterial strains UM1, UM8, and UM35 showed P-solubilization, whereas UM8 and UM35 exhibited 1-aminocyclopropane-1-carboxylate deaminase activity and indole acetic acid (IAA) production, respectively. The bacterial strains were inoculated on Brassica juncea plants cultivated in Cd and salt-affected soils due to the above PGP activities and stress tolerance. Plants inoculated with the bacterial strains B. cereus and B. megaterium significantly (p < 0.05) increased shoot fresh weight (17 ± 1.17-29 ± 0.88 g/plant), shoot dry weight (2.50 ± 0.03-4.40 ± 0.32 g/plant), root fresh weight (7.30 ± 0.58-13.30 ± 0.58 g/plant), root dry weight (0.80 ± 0.04-2.00 ± 0.01 g/plant), and shoot K contents (62.76 ± 1.80-105.40 ± 1.15 mg/kg dwt) in normal and stressful conditions. The bacterial strain B. megaterium significantly (p < 0.05) decreased shoot Na+ and Cd++ uptake in single and dual stress conditions. Both bacterial strains, E. aestuarii and B. cereus, efficiently reduced Cd++ translocation and bioaccumulation in the shoot. Bacterial inoculation improved the uptake of K+ and Ca++, while restricted Na+ and Cd++ in B. juncea shoots indicated their potential to mitigate the dual stresses of salt and Cd in B. juncea through ion homeostasis.

Repurposing of investigational cancer drugs: Early phase discovery of dengue virus NS2B/NS3 protease inhibitors.

Dengue fever is a neglected vector-borne disease and is more prevalent in Asia. Currently, no specific treatment is available. Given the time and cost of de novo drug discovery and development, an alternative option of drug repurposing is becoming an effective tool. We screened a library of 1127 pharmacologically active, metabolically stable, and structurally diverse small anticancer molecules to identify inhibitors of the dengue virus (DENV) NS2B/NS3 protease. Enzyme kinetics and inhibition data revealed four B-cell lymphoma 2 inhibitors, that is, ABT263, ABT737, AT101, and TW37, as potent inhibitors of DENV NS2B/NS3 protease, with IC50 values of 0.86, 1.15, 0.81, and 0.89 µM, respectively. Mode of inhibition experiments and computational docking analyses indicated that ABT263 and ABT737 are competitive inhibitors, whereas AT101 and TW37 are noncompetitive inhibitors of the protease. With further evaluation, the identified inhibitors of the DENV NS2B/NS3 protease have the potential to be developed into specific anti-dengue therapeutics.

Leveraging Metaheuristic Unequal Clustering for Hotspot Elimination in Energy-Aware Wireless Sensor Networks.

Wireless sensor networks (WSNs) are becoming a significant technology for ubiquitous living and continue to be involved in active research because of their varied applications. Energy awareness will be a critical design problem in WSNs. Clustering is a widespread energy-efficient method and grants several benefits such as scalability, energy efficiency, less delay, and lifetime, but it results in hotspot issues. To solve this, unequal clustering (UC) has been presented. In UC, the size of the cluster differs with the distance to the base station (BS). This paper devises an improved tuna-swarm-algorithm-based unequal clustering for hotspot elimination (ITSA-UCHSE) technique in an energy-aware WSN. The ITSA-UCHSE technique intends to resolve the hotspot problem and uneven energy dissipation in the WSN. In this study, the ITSA is derived from the use of a tent chaotic map with the traditional TSA. In addition, the ITSA-UCHSE technique computes a fitness value based on energy and distance metrics. Moreover, the cluster size determination via the ITSA-UCHSE technique helps to address the hotspot issue. To demonstrate the enhanced performance of the ITSA-UCHSE approach, a series of simulation analyses were conducted. The simulation values stated that the ITSA-UCHSE algorithm has reached improved results over other models.