WNK kinases sense molecular crowding and rescue cell volume via phase separation.

When challenged by hypertonicity, dehydrated cells must recover their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless condensates, initiating a phosphorylation-dependent signal that drives net ion influx via the SLC12 cotransporters to restore cell volume. WNK1 condensate formation is driven by its intrinsically disordered C terminus, whose evolutionarily conserved signatures are necessary for efficient phase separation and volume recovery. This disorder-encoded phase behavior occurs within physiological constraints and is activated in vivo by molecular crowding rather than changes in cell size. This allows kinase activity despite an inhibitory ionic milieu and permits cell volume recovery through condensate-mediated signal amplification. Thus, WNK kinases are physiological crowding sensors that phase separate to coordinate a cell volume rescue response.

Assessment of growth, and ion uptake of plant species, Conocarpus erectus and Dodonaea viscosa, on industrial solid waste.

Present study assessed the growth of two plant species and ion uptake by them grown on different proportion of industrial solid waste and garden soil. The industrial waste having high concentration of chemicals were used with garden soil at different proportion i.e. 0% (T0), 5% (T1), 10% (T2), 15% (T3) and 20% (T4). Two species namely Conocarpus erectus (alien plant) and Dodonaea viscosa (indigenous) were used as test plants in pot study. Different parameters including growth, physiology, and anatomy of plants and concentration of cations (Na+, K+, Ca2+, and Mg2+) in the plant shoot and root were measured at different time duration (initial, 1st, 2nd, 3rd and 4th month). The key objective of the study was to use these plants to establish their plantations on the barren lands where industrial solid wastes were being disposed of. C. erectus showed better growth than D. viscosa, as well as more uptake of ions. A significant increase in plant growth was observed in fourth month in T1, where plant height reached 24.5% and 46% for C. erectus and D. viscosa, respectively. At harvest, in C. erectus, no significant difference in the fresh (65-78 g) and dry weight (24-30 g) of the shoot was observed across treatments compared to the control. In D. viscosa, at the time of harvest, the fresh and dry weights of the root and shoot showed a strong, significantly decreasing pattern across T1, T2, and T3, leading to the death of the plant at T3 and T4. Further, optimum ratio of waste soil to garden soil was found as 10:90 and 20:80 to establish the plantations of D. viscosa and C. erectus, respectively in areas where such solid waste from industries are disposed. Findings can be used for the restoration of such solid waste for the sustainable management of industrial areas and their associated ecosystems.

Serotype and genomic diversity of dengue virus during the 2023 outbreak in Pakistan reveals the circulation of genotype III of DENV-1 and cosmopolitan genotype of DENV-2.

Dengue, a mosquito-borne viral disease, poses a significant public health challenge in Pakistan, with a significant outbreak in 2023, prompting our investigation into the serotype and genomic diversity of the dengue virus (DENV). NS-1 positive blood samples from 153 patients were referred to the National Institute of Health, Pakistan, between July and October 2023. Among these, 98 (64.1%) tested positive using multiplex real-time PCR, with higher prevalence among males (65.8%) and individuals aged 31-40. Serotyping revealed DENV-1 as the predominant serotype (84.7%), followed by DENV-2 (15.3%). Whole-genome sequencing of 18 samples (DENV-1 = 17, DENV-2 = 01) showed that DENV-1 (genotype III) samples were closely related (>99%) to Pakistan outbreak samples (2022), and approx. > 98% with USA (2022), Singapore and China (2016), Bangladesh (2017), and Pakistan (2019). The DENV-2 sequence (cosmopolitan genotype; clade IVA) shared genetic similarity with Pakistan outbreak sequences (2022), approx. > 99% with China and Singapore (2018-2019) and showed divergence from Pakistan sequences (2008-2013). No coinfection with dengue serotypes or other viruses were observed. Comparisons with previous DENV-1 sequences highlighted genetic variations affecting viral replication efficiency (NS2B:K55R) and infectivity (E:M272T). These findings contribute to dengue epidemiology understanding and underscore the importance of ongoing genomic surveillance for future outbreak responses in Pakistan.

Molecular insights into expression and silencing of resistance determinants in Staphylococcus aureus.

OBJECTIVE: This study aimed to investigate the status of antimicrobial-resistant strains of Staphylococcus aureus in Pakistan, their association in terms of co-occurrence with the biofilm-forming genes, resistance profiling and associated discrepancies in diagnostic methods. METHODOLOGY: A total of 384 milk samples from bovine was collected by using convenient sampling technique and were initially screened for subclinical mastitis, further preceded by isolation and confirmation of S. aureus. The S. aureus isolates were subjected to evaluation of antimicrobial resistance by phenotypic identification using Kirby-Bauer disc diffusion method, while the genotypic estimation was done by polymerase chain reaction to declare isolates as methicillin, beta-lactam, vancomycin, tetracycline, and aminoglycoside resistant S. aureus (MRSA, BRSA, VRSA, TRSA, and ARSA), respectively. RESULTS: The current study revealed an overall prevalence of subclinical mastitis and S. aureus to be 59.11% and 46.69%, respectively. On a phenotypic basis, the prevalence of MRSA, BRSA, VRSA, TRSA, and ARSA was found to be 44.33%, 58.49%, 20.75%, 35.84%, and 30.18%, respectively. The results of PCR analysis showed that 46.80% of the tested isolates were declared as MRSA, 37.09% as BRSA, and 36.36% as VRSA, while the occurrence of TRSA and ARSA was observed in 26.31% and 18.75%, respectively. The current study also reported the existence of biofilm-producing genes (icaA and icaD) in 49.06% and 40.57% isolates, respectively. Lastly, this study also reported a high incidence of discrepancies for both genotypic and phenotypic identification methods of resistance evaluation, with the highest discrepancy ratio for the accA-aphD gene, followed by tetK, vanB, blaZ, and mecA genes. CONCLUSION: The study concluded that different antibiotic resistance strains of S. aureus are prevalent in study districts with high potential to transmit between human populations. The study also determined that there are multiple resistance determinants and mechanisms that are responsible for the silencing and expression of antibiotic resistance genes.

Genomic analysis and biodesulfurization potential of a new carbon-sulfur bond cleaving Tsukamurella sp. 3OW.

Direct combustion of sulfur-enriched liquid fuel oil causes sulfur oxide emission, which is one of the main contributors to air pollution. Biodesulfurization is a promising and eco-friendly method to desulfurize a wide range of thiophenic compounds present in fuel oil. Previously, numerous bacterial strains from genera such as Rhodococcus, Corynebacterium, Gordonia, Nocardia, Mycobacterium, Mycolicibacterium, Paenibacillus, Shewanella, Sphingomonas, Halothiobacillus, and Bacillus have been reported to be capable of desulfurizing model thiophenic compounds or fossil fuels. In the present study, we report a new desulfurizing bacterium, Tsukamurella sp. 3OW, capable of desulfurization of dibenzothiophene through the carbon-sulfur bond cleavage 4S pathway. The bacterium showed a high affinity for the hydrocarbon phase and broad substrate specificity towards various thiophenic compounds. The overall genome-related index analysis revealed that the bacterium is closely related to Tsukamurella paurometabola species. The genomic pool of strain 3OW contains 57 genes related to sulfur metabolism, including the key dszABC genes responsible for dibenzothiophene desulfurization. The DBT-adapted cells of the strain 3OW displayed significant resilience and viability in elevated concentrations of crude oil. The bacterium showed a 19 and 37% reduction in the total sulfur present in crude and diesel oil, respectively. Furthermore, FTIR analysis indicates that the oil's overall chemistry remained unaltered following biodesulfurization. This study implies that Tsukamurella paurometabola species, previously undocumented in the context of biodesulfurization, has good potential for application in the biodesulfurization of petroleum oils.

Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures: A Systemic Review and Meta-analysis.

OBJECTIVE: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer. METHODS: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups. RESULTS: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42). CONCLUSION: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.

Efficacy and Safety of Sphingosine 1-Phosphate Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy. METHODS: Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo. CONCLUSION: Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

Venous thromboembolic outcomes in patients with lymphedema and lipedema: An analysis from the National Inpatient Sample.

BACKGROUND: Patients with lymphedema and lipedema share physical exam findings that may lead to misdiagnosis. Poor mobility is common in patients with obesity and patients with lymphedema and lipedema. This may constitute a risk factor for venous thromboembolism (VTE). Our objective was to evaluate the association of VTE in obese patients with lymphedema and lipedema. METHODS: The National Inpatient Sample (NIS) was searched from 2016 to 2020 to identify hospital admissions of obese female patients with lymphedema and lipedema. Patients were analyzed in the context of presence or absence of VTE while adjusting for complex cluster sampling techniques. Predictors of VTE were accessed by multivariable regression. RESULTS: Lymphedema was identified in 189,985 patients and lipedema in 50,645 patients. VTE was observed in 3.12% (n = 374,210) of patients with obesity. In patients with obesity, VTE was more common in patients with lymphedema than without (2.6% vs 1.6%; p < 0.01). Similarly, VTE was more common in patients with lipedema than without (0.6% vs 0.4%; p < 0.01). After multivariable logistic regression, VTE events in obese patients with lymphedema were higher versus without (OR 1.6; CI 1.08-2.43; p = 0.02). Similarly, VTE events were more common in obese patients with lipedema versus obese patients without lipedema (OR 1.20; CI 1.03-1.41; p = 0.02). CONCLUSIONS: In this hypothesis-generating study, lymphedema and lipedema show a positive association with VTE after adjusting for baseline patient characteristics such as obesity, which is a known independent risk factor for VTE. Mechanisms whereby lymphedema and lipedema are associated with VTE should be investigated.

The therapeutic potential of isosakuranetin against perfluorooctane sulfonate instigated cardiac toxicity via modulating Nrf-2/Keap-1 pathway, inflammatory, apoptotic, and histological profile.

Perfluorooctane sulfonate (PFOS) is a pervasive organic toxicant that damages body organs, including heart. Isosakuranetin (ISN) is a plant-based flavonoid that exhibits a broad range of pharmacological potentials. The current investigation was conducted to evaluate the potential role of ISN to counteract PFOS-induced cardiac damage in rats. Twenty-four albino rats (Rattus norvegicus) were distributed into four groups, including control, PFOS (10 mg/kg) intoxicated, PFOS + ISN (10 mg/kg + 20 mg/kg) treated, and ISN (20 mg/kg) alone supplemented group. It was revealed that PFOS intoxication reduced the expressions of Nrf-2 and its antioxidant genes while escalating the expression of Keap-1. Furthermore, PFOS exposure reduced the activities of glutathione reductase (GSR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), Heme oxygenase-1 (HO-1) and glutathione (GSH) contents while upregulating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Besides, PFOS administration upregulated the levels of creatine kinase-MB (CK-MB), troponin I, creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Moreover, the levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were increased after PFOS intoxication. Additionally, PFOS exposure downregulated the expression of Bcl-2 while upregulating the expressions of Bax and Caspase-3. Furthermore, PFOS administration disrupted the normal architecture of cardiac tissues. Nonetheless, ISN treatment remarkably protected the cardiac tissues via regulating aforementioned dysregulations owing to its antioxidative, anti-inflammatory, and antiapoptotic properties.

An assessment of public experiences and expectations with physicians: a cross sectional study from Karachi, Pakistan.

BACKGROUND: Although physicians are highly regarded members of society, patients are not always satisfied with their care, suggesting a mismatch between the public's expectations and reality. Thus, the aim of this study was to determine the public's expectations regarding roles and responsibilities of a physician, to assess patient experiences, and to evaluate factors associated with the two outcomes. METHODS: A cross-sectional study was conducted via face-to-face structured interviews from July 14th to August 2nd, 2023, in Karachi, Pakistan. The study sample comprised 424 consenting adults enrolled by visiting public spaces (malls, parks, hospitals, and residential areas). A modified version of 'Exceptionally Good Doctor Likert scale', and 'Patient Picker-15' (PPE-15) questionnaires was used. The Likert and PPE-15 sections were scored through pre-decided criteria for expectations and experience, respectively, and categorized using a median cut-off into high and low expectations and negative and positive experiences, respectively for simple and multivariable logistic regression. RESULTS: A median score of 30.5/ 34 (IQR = 3.3) was found for expectations and 4/ 14 (IQR = 4) for experiences. Significant factors associated with expectations were older age groups (OR = 4.54 [1.18-17.50]) and higher monthly household incomes (0.40 [0.20-0.79]), while the odds of negative experiences were lower after visits to emergency departments (0.38 [0.18-0.84]) and private health care centers (0.31 [0.13-0.70]). CONCLUSION: These results suggest that the public has high expectations from physicians, however their experiences are not always positive. Initiatives to develop a patient-centric ethos are needed for which we outline recommendations to both the public and physicians, respectively.

Mitigative potential of kaempferide against polyethylene microplastics induced testicular damage by activating Nrf-2/Keap-1 pathway.

Polyethylene microplastics (PE-MPs) are one of the environmental contaminants that instigate oxidative stress (OS) in various organs of the body, including testes. Kaempferide (KFD) is a plant-derived natural flavonol with potential neuroprotective, hepatoprotective, anti-cancer, anti-oxidant and anti-inflammatory properties. Therefore, the present study was designed to evaluate the alleviative effects of KFD against PE-MPs-prompted testicular toxicity in rats. Fourty eight adult male albino rats were randomly distributed into 4 groups: control, PE-MPs-administered (1.5 mgkg-1), PE-MPs (1.5 mgkg-1) + KFD (20 mgkg-1) co-treated and KFD (20 mgkg-1) only treated group. PE-MPs intoxication significantly (P < 0.05) lowered the expression of Nrf-2 and anti-oxidant enzymes, while increasing the expression of Keap-1. The activities of anti-oxidants i.e., catalase (CAT), glutathione reductase (GSR), superoxide dismutase (SOD), hemeoxygene-1 (HO-1) and glutathione peroxidase (GPx) were reduced, besides malondialdehyde (MDA) and reactive oxygen species (ROS) contents were increased significantly (P < 0.05) following the PE-MPs exposure. Moreover, PE-MPs exposure significantly (P < 0.05) reduced the sperm motility, viability and count, whereas considerably (P < 0.05) increased the dead sperm number and sperm structural anomalies. Furthermore, PE-MPs remarkably (P < 0.05) decreased steroidogenic enzymes and Bcl-2 expression, while increasing the expression of Caspase-3 and Bax. PE-MPs exposure significantly (P < 0.05) reduced the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, whereas inflammatory indices were increased. PE-MPs exposure also induced significant histopathological damages in the testes. Nevertheless, KFD supplementation significantly (P < 0.05) abrogated all the damages induced by PE-MPs. The findings of our study demonstrated that KFD could significantly attenuate PE-MPs-instigated OS and testicular toxicity, due to its anti-oxidant, anti-inflammatory, androgenic and anti-apoptotic potential.

Amentoflavone mediated hepatoprotection to counteract paraquat instigated hepatotoxicity via modulating Nrf2/keap1 pathway: A biochemical, inflammatory, apoptotic and histopathological study.

Paraquat (PQ) is a ubiquitous and water-soluble herbicide which has potential to cause systematic poisoning. PQ intoxication is known to be associated with various clinical complications including hepatotoxicity. Amentoflavone (AMF) is an active phenolic compound that exhibits a broad range of biological as well as pharmacological activities. This study was designed to determine the hepato-protective potential of AMF against PQ instigated hepatotoxicity in rats. Forty-eight rats were distributed into four groups such as control group, PQ-treated group (5 mg/kg), PQ (5 mg/kg) + AMF (40 mg/kg) exposed group and AMF (40 mg/kg) only supplemented group. It was revealed that PQ exposure reduced nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidative genes expression whereas increase the expression of Kelch-like ECH-associated protein 1(Keap1). Besides, PQ intoxication reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), glutathione peroxidase (GPx), Heme- oxygenase-1 (HO-1) & glutathione (GSH) content. Furthermore, the levels of reactive oxygen species (ROS) & malondialdehyde (MDA) were increased. In addition, PQ significantly increased the hepatic serum enzymes including alkaline phosphatase (ALP), aspartate transaminase (AST), & alanine transaminase (ALT) along with inflammatory biomarkers levels such as tumor necrosis- α (TNF- α), nuclear factor- κB (NF-κB), interleukin-6 (IL-6), interleukin 1beta (IL-1ß), & cyclo­oxygenase-2 (COX-2) activity. PQ intoxication increased the expressions of pro-apoptotic markers i.e., Bcl-2-associated X protein (Bax) & Cysteine-aspartic protease-3 (Caspase-3) while reducing the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl-2). Furthermore, PQ intoxication prompted various histopathological impairments. However, the co-administration of AMF significantly improved the abovementioned hepatic damages induced by PQ. The present study indicated that AMF may be an effective therapeutic candidate to mitigate PQ provoked hepatic impairments due to its anti-apoptotic, antioxidant & anti-inflammatory properties.

Coenzyme Q10 improves the quality and in vitro fertility of post-thawed buffalo (Bubalus bubalis) semen via its antioxidative effect.

This study aimed to determine the effects of Coenzyme Q10 (CoQ10) in the freezing medium on functional and oxidative stress parameters and in vitro fertilization (IVF) rate of buffalo sperm. Collected samples were relocated to the laboratory for initial evaluation, gentle dilution in extenders, cooling (4°C, 2 h), equilibration (4°C, 4 h), packaging (straws, 0.5 mL), programmable freezing, and thawing (37°C, 30 s). Statistical analysis depicted that adding CoQ10 (100 µM) in a freezing medium caused a significant augmentation in total motility (%), average path, and straight-line velocities (µm/sec) of buffalo sperm than control. Adding CoQ10 (100 µM) improved sperm progressive motility, rapid velocity, and functional parameters (%) compared to the control and 10 µM of CoQ10. Moreover, CoQ10 in a freezing medium caused a significant augmentation in seminal plasma catalase (U/mL) and glutathione reductase (GSH; nmol/109 ) at 100 µM than control and other treatments. CoQ10 inclusion (100 µM) ameliorates seminal plasma superoxide dismutase (U/mL), glutathione-S-transferase (GST; nmol/mL/min) fructose (µg/mL), and ATP (nmol/million) than control. Furthermore, CoQ10 at 100 µM improved seminal plasma glutathione peroxidase (µM) levels than control, 10 µM, and 20 µM. Lastly, hydrogen peroxide (H2 O2; nM) production was significantly lower at 100 µM than at control and 10 µM. CoQ10 (100 µM) caused a significant augmentation in the un-capacitated pattern followed by a reduction in the capacitated pattern, and apoptosis-like changes (%) than control, and other treatments, whereas viability was increased than control and other treatments. CoQ10 (100 µM) significantly improved the IVF rate in comparison with control, CoQ10 at 10 µM, and 20 µM groups. In conclusion, the addition of CoQ10 (100 µM) in the freezing medium can improve the quality and in vitro fertility of post-thawed buffalo semen via its antioxidative effect. Further studies are needed to evaluate the effect of CoQ10 on the in vivo fertility of buffalo bull semen.

Sudachitin Alleviates Paraquat Instigated Testicular Toxicity in Albino Rats via Regulating Nrf-2/Keap-1, Inflammatory, Steroidogenic, and Histological Profile.

Paraquat (PQ) is a noxious herbicide which adversely affects the vital organs including male reproductive system. Sudachitin (SCN) is a naturally occurring flavonoid that demonstrates a wide range of biological potentials. The current study was designed to investigate the alleviative potential of SCN to avert PQ-induced testicular toxicity in rats. Forty-eight male rats (Rattus norvegicus) were apportioned into four groups including control, PQ (5 mg/kg), PQ + SCN (5 mg/kg + 30 mg/kg), and SCN (30 mg/kg) only treated group. Our findings elucidated that PQ treatment reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and its antioxidant genes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR) and glutathione peroxidase (GPx), while elevating the levels of reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, PQ intoxication upregulated the expressions of Keap-1 while downregulating the expression of 3-beta hydroxysteroid dehydrogenase (3ß-HSD), 17-beta hydroxysteroid dehydrogenase (17ß-HSD), and steroidogenic acute regulatory protein (StAR). Moreover, sperm anomalies were increased following the exposure to PQ. Besides, PQ exposure decreased the levels of plasma testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) while increasing the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-1beta (IL-1ß), and cyclooxygenase-2 (COX-2). Additionally, PQ treatment escalated the expressions of cysteinyl aspartate-specific proteases-3 (Caspase-3) and Bcl-2-associated X-protein (Bax) while downregulating the expressions of B-cell lymphoma-2 (Bcl-2). Furthermore, PQ exposure disrupted the normal architecture of testicular tissues. However, SCN treatment remarkably protected the testicular tissues via regulating the aforementioned disruptions owing to its antioxidant, anti-inflammatory, and androgenic potential.

Genotypic insights to Panton-Valentine leukocidin positive methicillin-resistant Staphylococcus aureus isolated from cattle mastitis.

In this research communication we investigate the prevalence and antimicrobial susceptibility of S. aureus harboring virulent genes responsible for mastitis in cattle of Punjab, Pakistan. A total of 690 milk samples were collected from commercial dairy farms for analysis of the prevalence of subclinical and clinical mastitis and isolation of S. aureus. Virulence ability and methicillin resistance in S. aureus (MRSA) was determined by targeting the pvl (the gene for Panton-Valentine leukocidin) and mecA genes, respectively. A total of 175 S. aureus isolates exhibiting prevalence of pvl gene (6.28%) and mecA gene (22.28%) were determined. Antimicrobial susceptibility testing of pvl positive and negative MRSA against different classes of antibiotics revealed 100% resistance against ß-lactams while 100% sensitivity towards tylosin and linezolid.

Multilevel Pain Assessment with Functional Near-Infrared Spectroscopy: Evaluating ΔHBO2 and ΔHHB Measures for Comprehensive Analysis.

Assessing pain in non-verbal patients is challenging, often depending on clinical judgment which can be unreliable due to fluctuations in vital signs caused by underlying medical conditions. To date, there is a notable absence of objective diagnostic tests to aid healthcare practitioners in pain assessment, especially affecting critically-ill or advanced dementia patients. Neurophysiological information, i.e., functional near-infrared spectroscopy (fNIRS) or electroencephalogram (EEG), unveils the brain's active regions and patterns, revealing the neural mechanisms behind the experience and processing of pain. This study focuses on assessing pain via the analysis of fNIRS signals combined with machine learning, utilising multiple fNIRS measures including oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB). Initially, a channel selection process filters out highly contaminated channels with high-frequency and high-amplitude artifacts from the 24-channel fNIRS data. The remaining channels are then preprocessed by applying a low-pass filter and common average referencing to remove cardio-respiratory artifacts and common gain noise, respectively. Subsequently, the preprocessed channels are averaged to create a single time series vector for both ΔHBO2 and ΔHHB measures. From each measure, ten statistical features are extracted and fusion occurs at the feature level, resulting in a fused feature vector. The most relevant features, selected using the Minimum Redundancy Maximum Relevance method, are passed to a Support Vector Machines classifier. Using leave-one-subject-out cross validation, the system achieved an accuracy of 68.51%±9.02% in a multi-class task (No Pain, Low Pain, and High Pain) using a fusion of ΔHBO2 and ΔHHB. These two measures collectively demonstrated superior performance compared to when they were used independently. This study contributes to the pursuit of an objective pain assessment and proposes a potential biomarker for human pain using fNIRS.

Chemical Composition, Repellent, and Oviposition Deterrent Potential of Wild Plant Essential Oils against Three Mosquito Species.

In this study, the chemical composition, repellent, and oviposition deterrent effects of five plant essential oils (EOs) extracted from Lantana camara (Verbenaceae), Schinus terebinthifolia (Anacardiaceae), Callistemon viminalis (Myrtaceae), Helichrysum odoratissimum (Asteraceae), and Hyptis suaveolens (Lamiaceae) were evaluated against Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus. When tested at 33.3 µg/cm2, L. camara, S. terebinthifolia, C. viminalis, and H. odoratissimum were effective repellents against Ae. aegypti (89%, 91%, 90%, and 51% repellency, respectively), but they were less repellent against An. gambiae (66%, 86%, 59%, and 49% repellency, respectively). Interestingly, L. camara, S. terebinthifolia, C. viminalis, and H. odoratissimum exhibited 100% repellency against Cx. quinquefasciatus at 33.3 µg/cm2. In time-span bioassays performed at 333 µg/cm2, the EO of L. camara exhibited 100% repellence against Ae. aegypti and An. gambiae for up to 15 min and against Cx. quinquefasciatus for 75 min. The oviposition bioassays revealed that L. camara exhibited the highest activity, showing 85%, 59%, and 89% oviposition deterrence against Ae. aegypti, An. gambiae, and Cx. quinquefasciatus, respectively. The major compounds of L. camara, S. terebinthifolia, and C. viminalis were trans-ß-caryophyllene (16.7%), α-pinene (15.5%), and 1,8-cineole (38.1%), respectively. In conclusion, the L. camara and S. terebinthifolia EOs have the potential to be natural mosquito repellents.

Hydrochemical, hydrogeological, and cancer health risk analysis of groundwater due to anthropogenic activities, Hasilpur, Pakistan.

Drinking water quality deteriorates rapidly due to anthropogenic activities and rapid population growth. These activities, in developing countries, will lead to water scarcity. In Pakistan, 70% of the population has no access to safe water, and people use canal water to drink. This study performed hydrochemical, hydrogeological, and cancer risk analyses on Tahsil Hasilpur, Bahawalpur, Pakistan. Thirteen tube wells were selected for groundwater and borehole log study. Twenty-two drinking water quality parameters were analyzed using standard methods and quality checks. The borehole data (2D and 3D) shows the abundance of sand (fine and coarse) with some uniformities, which changes the groundwater quality. The results of water quality parameters show that the concentration of TDS (2064-11,159 mg/L), Cl-1 (213-4917 mg/L), As+3 (0.048-0.158 mg/L), Pb+2 (1.294-1.673 mg/L), and Cd+2 (0.008-0.053 mg/L) were beyond guideline values. The statistical analysis showed that the parameters have a moderate to strong correlation (Pearson correlation), which may be due to the same origin (ANOVA). The principal component analysis and cluster analysis confirm the multiple sources of pollutants in the groundwater of the study area. The Piper, Durov, Stiff, and Scholler diagrams confirm that the groundwater system has an abundance of Ca+2 and Mg+2 with Cl-1. The Gibbs diagram showed that the groundwater is not saturated and tends to dissolve more minerals. The hazard quotient values are above 1.0, which indicates noncancer risk severity. The HQ trend was As+3 > Pb+2 > Cd+2 > Ni+2 > Cu+2 > Cr+2 > Zn+2 > Fe+2. The cancer risk values showed that 3-5 people/100 population were exposed to cancer risk. The trend of CR was As+3 > Cd+2 > Cr+2 > Pb+2 > Ni+2. The GIP mapping of pollutants showed that the concentration of pollutants near the canals was high compared to the locations away from the canal. The overall groundwater quality is alarming and needs immediate government attention.

Design and performance assessment of modular multi-band photonic-integrated WSS.

Today, optical transport and data center networks extensively utilize photonic integrated systems due to their large bandwidth and a high degree of reconfigurability. In addition to these properties, photonic integrated-based systems can deliver an overall low fabrication cost, a small footprint, and low power consumption. In this perspective, we present a modular photonic integrated multi-band wavelength selective switch (WSS) capable of managing a wide spectrum, covering the three S+C+L bands, and potentially scalable to larger numbers of output fibers and routed channels. We propose a complete description of the device starting from the physical level, commenting on the device's internal structure and design-related issues. Then, we move to the transmission level, providing a complete abstraction of the proposed WSS in the context of software-defined optical networks by providing a deterministic model to evaluate the routing controls, thermal spectral tunability, and the quality of transmission degradation. Finally, a transmission scenario operating on 400ZR standards and a network case study are also demonstrated to evaluate the performance of the proposed WSS in a single or multistage cascade setup.

On-farm epidemiology, virulence profiling, and molecular characterization of methicillin-resistant Staphylococcus aureus at goat farms.

Antimicrobial resistance (AMR) becomes a challenging issue that limits the therapeutic options for both veterinary and public health professionals. The current study aimed to investigate the on-farm epidemiology, antibiotics resisting profiling, virulence analysis, and molecular detection of methicillin-resistant Staphylococcus aureus (MRSA) at the caprine-human interface. A total of 768 goat milk samples and 94 skin swabs from farm personnel were collected from 30 goat flocks and processed for isolation of S. aureus. The study isolates were confirmed as MRSA based on the oxacillin and cefoxitin disc diffusion test and the presence of mecA gene. MRSA isolates of goats and human origin were characterized and further evaluated for the presence of virulence genes responsible for intramammary infections and public health hazards. The results revealed 26.82 % and 27.79 % goat milk samples and human samples positive for S. aureus, respectively. A higher MRSA prevalence of 35.92 % and 10.71 % was found in goat and human isolates respectively. The phylogenetic analysis revealed a lesser extent of homology in mecA gene of S. aureus isolates at the caprine-human interface. Moreover, this study revealed strong evolutionary connection between the study isolates and MRSA isolates of Pakistani cattle and buffalo while the in-silico protein analysis showed that all sequences have the same protein motifs resembling penicillin binding protein 2a. The risk factors analysis revealed that teat length, drainage system, hygienic measures during milking, use of teat dip, teat injury, and veterinary services were significantly associated with subclinical mastitis in goats. A total of 43.24 % of local MRSA isolates showed multi-drug resistance (MDR). The isolates showed higher resistance to oxytetracycline followed by gentamicin and vancomycin while moxifloxacin, and linezolid were among the susceptible antibiotics. Local MRSA isolates carried virulence markers (nuc and coag genes) and biofilm-associated icaA (43.24 %) and icaD (29.73 %) genes which are responsible for the intramammary infection. The local isolates also carried the virulence genes of public health concern including the enterotoxin C (sec) gene (24.3 %), enterotoxins B (seb) gene (5.41 %), and enterotoxin D (sed) gene (2.7 %). Enterotoxins A (sea) and E (see) genes were not detected in any isolate. The study concluded that MRSA is an emerging and prevailing pathogen in dairy goats with a high potential to transmit to associated human beings. The presence of a variety of virulence factors as well as the associated antibiotic resistance makes MRSA a potential threat at animal-human interface and thus demands further research.