Co-occurrence of Tuberculous Meningitis and Intestinal Perforation in Abdominal Tuberculosis (TB): A Report of a Rare Case From Pakistan.

Tuberculosis (TB) remains a significant global health concern, with millions affected worldwide each year. Extrapulmonary TB, particularly involving the digestive tract and central nervous system, poses distinctive difficulties in both diagnosis and treatment. We report a case involving a 15-year-old girl with a history of intestinal TB on anti-tuberculous therapy who presented with symptoms suggestive of meningitis, along with abdominal pain and distension. Our initial suspicion was tuberculous meningitis, considering the underlining abdominal TB, which was later supported by cerebrospinal fluid analysis showing lymphocytic-predominant pleocytosis and positive acid-fast bacilli staining. Concurrently, the patient developed hemodynamic instability and severe abdominal pain, which on repeat X-rays of the abdomen showed air under the diaphragms, prompting surgical exploration and revealing multiple ileal perforations. Histopathological examination confirmed TB as the cause of perforation. This case highlights the diagnostic and therapeutic complexities of concurrent tuberculous meningitis and intestinal TB perforation. Early recognition and interdisciplinary management are crucial for optimal patient outcomes.

Engineering gold nanoworms with tunable longitudinal plasmon peak in the near infrared and their refractive index sensing properties.

The plasmonic properties of rod-shaped Au nanoparticles make them promising for numerous applications. The synthesis recipes for Au nanorods are well established and their longitudinal plasmon peak can be tuned over a wide wavelength range. Herein, we demonstrate that the longitudinal plasmon peak of gold NWs (NWs), which are bent nanorods, can be finely tuned in the near-infra-red region. The NWs were synthesized using a one-step reaction method. We have seen that the length and aspect ratio of NWs can be tuned by simply changing the pH of the reaction medium. Under higher pH reaction conditions, NWs with relatively smaller sizes were obtained. Similar to nanorods, NWs have a well-defined longitudinal plasmon peak, which scales linearly with their aspect ratio. Finite element analysis was used to model the optical properties of Au NWs. The simulated results matched well with the experimental spectra. The synthesized NWs have shown good refractive index sensitivities (RIS). The RIS of NWs increased with an increase in their aspect ratio. A maximum sensitivity value of 542 nm per RIU, was obtained for NWs with the plasmon peak at 1033 nm. The RIS values are comparable to that of Au nanorods and bipyramids.

Moyamoya Disease with Non-Functional Pituitary Macroadenoma: A Case Report of a Rare Presentation.

Moyamoya disease (MMD) is a rare neurological condition characterized by brain blood vessel narrowing, leading to collateral vessel formation. Diagnosis typically involves cerebral angiography and magnetic resonance angiography (MRA), with surgical revascularization often providing superior outcomes. Here, we present the case of a 55-year-old woman with hypertension, diabetes, and a history of ischemic stroke. She recently experienced a hemorrhagic stroke due to MMD, compounded by a non-functional pituitary macroadenoma. Recognizing signs of a hemorrhagic stroke is crucial to prevent future occurrences and ensure optimal outcomes. However, our understanding of the connection between MMD and pituitary macroadenoma remains incomplete. Further research is essential to refine diagnostic techniques and treatment strategies. Through continued research and awareness, we can strive for improved outcomes and an enhanced quality of life for individuals affected by MMD and its complications.

Evaluation of irrigation, drinking, and risk indices for water quality parameters of alpine lakes.

Alpine lakes are aquatic ecosystems that maintain and regulate water supply for the downstream streams, rivers, and other reservoirs. This study examined the water characteristics of various alpine lakes in Gilgit-Baltistan, Northern Pakistan. For this purpose, water was sampled and investigated for basic parameters, anions, and cations using the multi-parameter analyzers and atomic absorption spectrophotometer. Physicochemical parameters of alpine lakes were noted under the World Health Organization water guidelines, except for fluoride (F-) and turbidity in 4.3% and 36% of samples, respectively. Water quality index (WQI) classified samples (93%) as excellent and good quality (7%). Results showed maximum chronic daily intake values (0.14 ± 0.01 mg/kg-day) for nitrate (NO3-) and hazard quotient (0.80 ± 0.24) for F- in children via water intake from Upper Kachura and Shausar Lakes, respectively. Statistical analyses of Piper and Gibbs's plots revealed that the water quality is mainly characterized by bedrock geology.

Comprehensive Analysis of Salmonella Species Antibiogram and Evolving Patterns in Empirical Therapy: Insights From Tertiary Care Hospitals in Peshawar, Pakistan.

Background Typhoid fever presents a significant challenge in developing nations, exacerbated by the emergence of antibiotic-resistant strains due to widespread prevalence and overuse of antibiotics. This study seeks to assess the antibiogram profiles of Salmonella species isolated from blood cultures of patients hospitalized at two prominent tertiary care hospitals in Peshawar, Pakistan: Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC). By examining these profiles, the research aims to provide valuable insights into the evolving landscape of antibiotic resistance in the context of typhoid fever management. Materials and Methods This retrospective cross-sectional study utilized data gathered from two hospitals in Peshawar, KTH and HMC. Cases of enteric fever were identified based on positive blood cultures for Salmonella species. The study encompasses demographic information, seasonal prevalence, and antibiogram profiles of 3,137 cases that were presented between 2017 and 2023. Results Among the total 3,137 cases, males accounted for the majority, comprising 63% (2,044 cases). Particularly notable was the clustering of cases among children and adolescents aged one to 24 years. The incidence peaked during the months of summer and spring, from April to September. In terms of Salmonella Typhi isolates, considerable resistance was noted against first-line antibiotics such as amoxicillin/clavulanate (80.1%), co-trimoxazole/trimethoprim-sulfamethoxazole (66.6%), and chloramphenicol (86.9%), as well as against ceftriaxone (79.7%) and ciprofloxacin (51.6%). Conversely, certain antibiotics displayed higher sensitivity patterns, including meropenem (97.8%), doripenem (99.5%), imipenem (97.7%), ertapenem (96.5%), polymyxin B (99.4%), colistin (98.1%), and tigecycline (97.3%). Despite a limited sample size of 214 specimens, fosfomycin demonstrated a remarkable sensitivity of 93.4%. Sensitivities of amikacin and gentamicin were 90.7% and 81.5%, respectively. However, the sensitivity of azithromycin was concerning, standing at 66.5%. The antibiogram pattern for Salmonella exhibited significant and drastic changes. Conclusion In conclusion, this study sheds light on a higher prevalence of typhoid fever among males, with a notable seasonal peak observed during the summer and spring months. The age group most affected spans from one to 24 years. Salmonella isolates displayed significant resistance to conventional first-line antibiotics, alongside ciprofloxacin and third-generation cephalosporins. Azithromycin exhibited lower sensitivity compared to amikacin, gentamicin, and fosfomycin. The research advocates for the empirical use of amikacin, gentamicin, fosfomycin, and meropenem in the treatment of typhoid fever in Pakistan. Urgent measures, including regular Salmonella antibiogram surveillance, antibiotic stewardship, public health education, and Salmonella vaccination programs, are deemed crucial for primary disease prevention.

Comparison of the Latarjet Procedure With the Modified Putti-Platt Surgery for Recurrent Anterior Shoulder Dislocation With Respect to Functional Outcome.

Introduction Shoulder dislocation is the most common injury encountered in orthopedic outpatient department. The choice of procedure depends on the expertise of surgeons. The objective of this study was to compare the Latarjet procedure with the modified Putti-Platt surgery for recurrent anterior shoulder dislocation in terms of functional outcomes. Materials and methods A quasi-experimental study evaluated 60 patients with recurrent anterior shoulder instability. Patients were assigned to either Latarjet or modified Putti-Platt surgery. Functional outcomes were assessed at six months using the Constant-Murley shoulder score. Results This study encompassed 60 patients (mean age: 23.93±5.88 years) undergoing shoulder procedures. Functional outcomes exhibited a majority of 55% excellent, 35% good, 6.7% fair, and 3.3% poor outcomes. No significant differences in functional outcomes were found between the procedures. Conclusion Both procedures may be viable options for recurrent shoulder instability. The choice may depend on patient factors and surgeon preference. Further research is needed to refine techniques and identify ideal candidates.

Asymptomatic Salmonella Myocarditis: A Case Report of a Rare Entity.

Enteric fever typically displays symptoms like high fever, abdominal pain, constipation, and headaches, primarily affecting the digestive system. While it is commonly seen as a gastrointestinal infection, it can also lead to rare but significant cardiovascular issues. There have been only a few reported cases of enteric fever causing heart manifestations. We present a case of a young male with enteric fever-induced myocarditis, which, due to its rarity, can be challenging to diagnose and is essentially a diagnosis of exclusion. Cardiac MRI (CMR) is crucial for diagnosis, supported by ECG, echocardiograms, and troponin levels. The treatment involves standard approaches for cardiomyopathy, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and diuretics. However, our patient presented as a case of asymptomatic myocarditis and fully recovered with treatment without any long-lasting heart problems. Our study aims to contribute to the limited body of knowledge on heart-related complications of enteric fever, raising awareness among clinicians of such presentations in enteric fever cases.

Constructing copper Phthalocyanine/Molybdenum disulfide (CuPc/MoS2) S-scheme heterojunction with S-rich vacancies for enhanced Visible-Light photocatalytic CO2 reduction.

Constructing a heterojunction by combining two semiconductors with similar band structures is a successful approach to obtaining photocatalysts with high efficiency. Herein, a CuPc/DR-MoS2 heterojunction involving copper phthalocyanine (CuPc) and molybdenum disulfide with S-rich vacancies (13.66%) is successfully prepared by the facile hydrothermal method. Experimental results and theoretical calculations firmly demonstrated that photoelectrons exhibit an S-scheme charge transfer mechanism in the CuPc/DR-MoS2 heterojunction. The S-scheme heterojunction system has proven significant advantages in promoting the charge separation and transfer of photogenerated carriers, enhancing visible-light responsiveness, and achieving robust photoredox capability. As a result, the optimized 3CuPc/DR-MoS2 S-scheme heterojunction exhibits photocatalytic yields of CO and CH4 at 200 and 111.6 µmol g-1h-1, respectively. These values are four times and 4.5 times greater than the photocatalytic yields of pure DR-MoS2. This study offers novel perspectives on the advancement of innovative and highly effective heterojunction photocatalysts.

Systematic review on antibacterial photodynamic therapeutic effects of transition metals ruthenium and iridium complexes.

The prevalence of antibiotic-resistant pathogenic bacteria poses a significant threat to public health and ranks among the principal causes of morbidity and mortality worldwide. Antimicrobial photodynamic therapy is an emerging therapeutic technique that has excellent potential to embark upon antibiotic resistance problems. The efficacy of this therapy hinges on the careful selection of suitable photosensitizers (PSs). Transition metal complexes, such as Ruthenium (Ru) and Iridium (Ir), are highly suitable for use as PSs because of their surface plasmonic resonance, crystal structure, optical characteristics, and photonics. These metals belong to the platinum family and exhibit similar chemical behavior due to their partially filled d-shells. Ruthenium and Iridium-based complexes generate reactive oxygen species (ROS), which interact with proteins and DNA to induce cell death. As photodynamic therapeutic agents, these complexes have been widely studied for their efficacy against cancer cells, but their potential for antibacterial activity remains largely unexplored. Our study focuses on exploring the antibacterial photodynamic effect of Ruthenium and Iridium-based complexes against both Gram-positive and Gram-negative bacteria. We aim to provide a comprehensive overview of various types of research in this area, including the structures, synthesis methods, and antibacterial photodynamic applications of these complexes. Our findings will provide valuable insights into the design, development, and modification of PSs to enhance their photodynamic therapeutic effect on bacteria, along with a clear understanding of their mechanism of action.

Efficacy of Endopyelotomy for Secondary Pelvi-Ureteric Junction (PUJ) Obstruction in Terms of Improvement in Renal Function.

Objective The objective of this study is to measure renal function improvement after endopyelotomy for secondary pelvi-ureteric junction (PUJ) obstruction using technetium-99m diethylene-triamine-pentaacetate (DTPA) renal scintigraphy. Material and methods This descriptive study was carried out at the Department of Urology, Institute of Kidney Diseases, Peshawar, Pakistan from June 1, 2021, to May 31, 2023. The study included 118 secondary PUJ blockage patients who underwent endopyelotomy. Patient demographics, clinical history, and preoperative imaging findings were obtained. DTPA renal scintigraphy assessed renal function improvement postoperatively at intervals to determine the efficacy of endopyelotomy. Results The majority of the patients included in the study were male (n=65, 55.1%). The average age of the patients was 45.2 years, with the majority falling within the age range of 46-60 years (n=42, 35.6%). All patients had ultrasonography and computed tomography imaging done, and preoperative renal functions were obtained. Comorbidities included hypertension in 32 (27.12%) and diabetes in 18 (15.25%). DTPA renal scintigraphy showed improved renal function in 81.35% of patients at three months, 88.13% at six months, and 83.05% at 12 months; 15.3% of patients needed further treatments, and 5.1% had PUJ blockage recurrence. Conclusion This study offers significant insights into the results and complexities of endopyelotomy in patients suffering from PUJ blockage. The findings indicate that the technique efficiently enhances kidney function and alleviates symptoms in most patients. However, the study also emphasizes the need to monitor patients undergoing this procedure.

Concomitant Salmonella and Leptospira Meningitis: A Rare Case Report.

This study presents a unique case of concurrent salmonella and Leptospira meningitis in a 20-year-old woman with no prior medical history. Coinfection with endemic pathogens is plausible, especially in regions like Pakistan. While Salmonella meningitis is uncommon, it presents a significant medical emergency, particularly in immunocompromised adults. Neuroleptospirosis, though rare, can manifest in certain cases. The patient displayed persistent high fever, confusion, irritability, and a single seizure episode. Initial tests, including blood and cerebrospinal fluid (CSF) cultures and serological examinations, detected Salmonella typhi and positive leptospiral antibodies, respectively. Leptomeningeal enhancement was confirmed by an MRI. Treatment with azithromycin, meropenem, and ceftriaxone led to improvement after seven days. She was advised to complete a 28-day course for Salmonella meningitis. This case emphasizes the importance of considering multiple infectious causes, especially in endemic regions. Timely and thorough diagnostic evaluation, followed by appropriate antimicrobial therapy, is essential for effective management. Further research is warranted to enhance understanding of the epidemiology, clinical features, and optimal treatment strategies for such dual infections.

Prognostic Value of Multiplexed Assays of Variant Effect and Automated Patch-clamping for KCNH2-LQTS Risk Stratification.

Background: Long QT syndrome (LQTS) is a lethal arrhythmia condition, frequently caused by rare loss-of-function variants in the cardiac potassium channel encoded by KCNH2. Variant-based risk stratification is complicated by heterogenous clinical data, incomplete penetrance, and low-throughput functional data. Objective: To test the utility of variant-specific features, including high-throughput functional data, to predict cardiac events among KCNH2 variant heterozygotes. Methods: We quantified cell-surface trafficking of 18,323 variants in KCNH2 and recorded potassium current densities for 506 KCNH2 variants. Next, we deeply phenotyped 1150 KCNH2 missense variant patients, including ECG features, cardiac event history (528 total cardiac events), and mortality. We then assessed variant functional, in silico, structural, and LQTS penetrance data to stratify event-free survival for cardiac events in the study cohort. Results: Variant-specific current density (HR 0.28 [0.13-0.60]) and estimates of LQTS penetrance incorporating MAVE data (HR 3.16 [1.59-6.27]) were independently predictive of severe cardiac events when controlling for patient-specific features. Risk prediction models incorporating these data significantly improved prediction of 20 year cardiac events (AUC 0.79 [0.75-0.82]) over patient-only covariates (QTc and sex) (AUC 0.73 [0.70-0.77]). Conclusion: We show that high-throughput functional data, and other variant-specific features, meaningfully contribute to both diagnosis and prognosis of a clinically actionable monogenic disease.

Molecular modulation of interfaces in a Z-scheme van der Waals heterojunction for highly efficient photocatalytic CO2 reduction.

The construction of van der Waals (vdW) heterojunctions is a key approach for efficient and stable photocatalysts, attracting marvellous attention due to their capacity to enhance interfacial charge separation/transfer and offer reactive sites. However, when a vdW heterojunction is made through an ex-situ assembly, electron transmission faces notable obstacles at the components interface due to the substantial spacing and potential barrier. Herein, we present a novel strategy to address this challenge via wet chemistry by synthesizing a functionalized graphene-modulated Z-scheme vdW heterojunction of zinc phthalocyanine/tungsten trioxide (xZnPc/yG-WO3). The functionalized G-modulation forms an electron "bridge" across the ZnPc/WO3 interface to improve electron transfer, get rid of barriers, and ultimately facilitating the optimal transfer of excited photoelectrons from WO3 to ZnPc. The Zn2+ in ZnPc picks up these excited photoelectrons, turning CO2 into CO/CH4 (42/22 µmol.g-1.h-1) to deliver 17-times better efficiency than pure WO3. Therefore, the introduction of a molecular "bridge" as a means to establish an electron transfer conduit represents an innovative approach to fabricate efficient photocatalysts designed for the conversion of CO2 into valued yields.

Innovative dual-active sites in interfacially engineered interfaces for high-performance S-scheme solar-driven CO2 photoreduction.

The realization of 2D/2D Van der Waals (VDW) heterojunctions represents an advanced approach to achieving superior photocatalytic efficiency. However, electron transfer through Van der Waals heterojunctions formed via ex-situ assembly encounters significant challenges at the interface due to contrasting morphologies and potential barriers among the nanocomposite substituents. Herein, a novel approach is presented, involving the insertion of a phosphate group between copper phthalocyanine (CuPc) and B-doped and N-deficient g-C3N4 (BDCNN), to design and construct a Van der Waals heterojunction labeled as xCu[acs]/yP-BDCNN. The introduction of phosphate as a charge modulator and efficient conduit for charge transfer within the heterojunction resulted in the elimination of spatial barriers and induced electron movement from BDCNN to CuPc in the excited states. Consequently, the catalytic central Cu2+ in CuPc captured the photoelectrons, leading to the conversion of CO2 to C2H4, CO and CH4. Remarkably, this approach resulted in a 78-fold enhancement in photocatalytic efficiency compared to pure BDCNN. Moreover the findings confirm that the 2D-2D 4Cu[acs]/9P-BDCNN sheet-like heterojunction effectively boosts photocatalytic activity for persistent pollutants such as methyl orange (MO), methylene blue (MB), rhodamine B (RhB), and tetracycline antibiotics (TCs). The introduction of "interfacial interacting" substances to establish an electron transfer pathway presents a novel and effective strategy for designing photocatalysts capable of efficiently reducing CO2 into valuable products.

Dual-polarized 8-port sub 6 GHz 5G MIMO diamond-ring slot antenna for smart phone and portable wireless applications.

This manuscript presents high performance dual polarized eight-element multiple input multiple output (MIMO) fifth generation (5G) smartphone antenna. The design consists of four dual-polarized microstrip diamond-ring slot antennas, positioned at corners of printed circuit board (PCB). Cheap Fr-4 dielectric with permittivity 4.3 and thickness of 1.6mm is used as substrate with overall dimension of 150 × 75 × 1.6 mm3. In mobile system due to limited space mutual coupling between nearby antenna elements is an issue that distort MIMO antenna performance. Defected ground structure is used to control coupling. The defected ground structure has advantages like ease of fabrication, compact size and high efficiency as compare to other techniques. Less than 30dB coupling is achieved for adjacent elements. The -10 dB impedance bandwidth of 700 MHz is achieved for all radiating elements ranging from 3.3 GHz to 4.1 GHz. The value is about 900MHz for -6dB. The proposed antenna offers good results in terms of fundamental antenna parameters like reflection coefficient, transmission coefficient, maximum gain, total efficiency. The antenna achieved average gain more than 3.8dBi and average radiation efficiency more than 80% for single dual polarized element. The antenna provides sufficient radiation coverage in all sides. The MIMO antenna characteristics like diversity gain (DG), envelope correlation coefficient (ECC), total active reflection coefficient (TARC) and channel capacity are calculated and found according to standards. Furthermore, effect of user on antenna performance in data-mode and talk-mode are studied. Proposed design is fabricated and tested in real time. The measured results shows that proposed design can be used in future smartphones applications. The design is compared with some of the existing work and found to be the best one in many parameters and can be used for commercial use.

Speech Emotion Recognition Using Convolution Neural Networks and Multi-Head Convolutional Transformer.

Speech emotion recognition (SER) is a challenging task in human-computer interaction (HCI) systems. One of the key challenges in speech emotion recognition is to extract the emotional features effectively from a speech utterance. Despite the promising results of recent studies, they generally do not leverage advanced fusion algorithms for the generation of effective representations of emotional features in speech utterances. To address this problem, we describe the fusion of spatial and temporal feature representations of speech emotion by parallelizing convolutional neural networks (CNNs) and a Transformer encoder for SER. We stack two parallel CNNs for spatial feature representation in parallel to a Transformer encoder for temporal feature representation, thereby simultaneously expanding the filter depth and reducing the feature map with an expressive hierarchical feature representation at a lower computational cost. We use the RAVDESS dataset to recognize eight different speech emotions. We augment and intensify the variations in the dataset to minimize model overfitting. Additive White Gaussian Noise (AWGN) is used to augment the RAVDESS dataset. With the spatial and sequential feature representations of CNNs and the Transformer, the SER model achieves 82.31% accuracy for eight emotions on a hold-out dataset. In addition, the SER system is evaluated with the IEMOCAP dataset and achieves 79.42% recognition accuracy for five emotions. Experimental results on the RAVDESS and IEMOCAP datasets show the success of the presented SER system and demonstrate an absolute performance improvement over the state-of-the-art (SOTA) models.

Characterization of Monoamine Oxidase-A in tropical liver fluke, Fasciola gigantica.

Fasciola gigantica, responsible for the zoonotic disease fasciolosis, pose a great threat to the livestock and human health worldwide. The triclabendazole (TCBZ) has been used for decades as a broad spectrum anthelmintic to control this perilous disease but the emergence of resistance in flukes against TCBZ has prompted researchers across the world to explore for new drugs and antigenic targets. World Health Organization has strongly recommended the utilization of neurobiologically significant biomolecules as new drug/antigenic targets because of their significant role in the physiology of parasites. Monoamine Oxidase (MAO) is an important neurobiological enzyme which catabolizes aminergic neurotransmitters thus preventing prolonged excitation of neurons and in non-neuronal cells it prevents cellular toxicity due to accumulation of toxic monoamines. Owing to the important role of MAO in the survival and perpetuation of parasites, multipronged approaches were undertaken for the characterization of MAO-A in F. gigantica. The activity of MAO was found to be 1.5 times higher in the mitochondrial samples than the whole homogenate samples. The adult worms of the F. gigantica appeared to possess both the isoforms of MAO i.e., MAO-A and MAO-B. The zymographic studies revealed strong enzyme activity in its native state as assessed through prominent dark bands at 250KDa in the zymogram. The enzyme was also found to be highly immunogenic as revealed by high antibody titer at 1:6400 dilution. The immunogenicity of MAO-A enzyme was further established in the Western Blots in which a strong band of 50KDa was distinctly evident. Despite ubiquitous presence of MAO in F. gigantica some regions like tegumental surface and intestinal caecae displayed strong immunofluorescence as compared to other regions. The detection of MAO-A in the F. gigantica samples in Dot-Blot assay indicate a great potential of this molecule for the immunodiagnostics of fasciolosis, particularly in the field conditions. The enzyme activity was sensitive to the specific inhibitor clorgyline in a concentration dependant manner, particularly in the late incubation period. The zymographic results also exhibited similar trend. The strong intensity of spots in Dot-blots indicate high immunogenicity of the MAO protein. The intensity of bands/spots in the samples of worms treated with clorgyline also declined, clearly indicating that the tropical liver fluke possesses prominent MAO-A activity.

Clinostomum complanatum: Anthelmintic potential of curcumin on the infective progenetic metacercarial stage.

The emerging resistance against commonly used antiparasitic drugs has driven investigators to explore alternative approaches using plant-derived active ingredients. These compounds have been tested for antiviral, antibacterial, and anthelmintic properties, particularly against adult worms. However, their effects on larval forms have been neglected. Curcumin is a polyphenol that is a significant constituent of the rhizome of Curcuma longa and possesses various biological activities, including antioxidant, anti-inflammatory, anti-infectious, and anti-carcinogenic. In the present study, the anthelmintic potential of curcumin was tested in vitro for its efficacy against the zoonotically important larval form, the progenetic metacercariae of Clinostomum complanatum, which were procured from the forage fish, Trichogaster fasciatus. Curcumin produced time and concentration-dependent inhibition in the motility of treated metacercarial worms, with the maximum inhibition of motility reported at 60 µM along with a significant increase of (36-92%) in ROS and (57-112%) in GSH levels at the end of a period of 6 h. In contrast, curcumin at the highest concentration significantly inhibited the activities of the antioxidant and detoxification enzymes SOD (36%) and GST (16%), respectively, in addition to altering the polypeptide profile and inhibiting cysteine proteases. The tegumental surface appeared to be highly disrupted in curcumin-treated worms, exhibiting severe blebbing, shearing of the tegument, and spine erosion. Such changes would affect the tegumental functions and survival of worms in the hostile microenvironment. This would render worms more susceptible to host-mediated rejection responses. Based on the results of the present study, it is inferred that C. complanatum could serve as an excellent model for screening novel anthelmintic drugs against larval trematodes of great economic significance. Furthermore, we conclude that curcumin could be exploited as an excellent phytotherapeutic agent against the virulent larval form under investigation.

Porcine reproductive and respiratory syndrome virus degrades DDX10 via SQSTM1/p62-dependent selective autophagy to antagonize its antiviral activity.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus devastating the global swine industry. DEAD-box helicases (DDXs) are a family of ATP-dependent RNA helicases that are predominantly implicated in modulating cellular RNA metabolism. Meanwhile, a growing number of studies have suggested that some DDXs are associated with innate immunity and virus infection, so they are considered potential antiviral targets. Herein, we screened 40 DDXs and found that ectopic expression of DDX10 exhibited a significant anti-PRRSV effect, while DDX10 knockdown promoted PRRSV proliferation. Further analysis revealed that DDX10 positively regulates type I interferon production, which may contribute to its anti-PRRSV effect. Interestingly, PRRSV infection promoted DDX10 translocation from the nucleus to the cytoplasm for macroautophagic/autophagic degradation to block the antiviral effect of DDX10. By screening PRRSV-encoded proteins, we found that the viral envelope (E) protein interacted with DDX10. In line with the autophagic degradation of DDX10 during PRRSV infection, E protein could induce autophagy and reduce DDX10 expression in wild-type cells, but not in ATG5 or ATG7 knockout (KO) cells. When further screening the cargo receptors for autophagic degradation, we found that SQSTM1/p62 (sequestosome 1) interacted with both DDX10 and E protein, and E protein-mediated DDX10 degradation was almost entirely blocked in SQSTM1 KO cells, demonstrating that E protein degrades DDX10 by promoting SQSTM1-mediated selective autophagy. Our study reveals a novel mechanism by which PRRSV escapes host antiviral innate immunity through selective autophagy, providing a new target for developing anti-PRRSV drugs.Abbreviations: ACTB: actin beta; ATG: autophagy related; co-IP: co-immunoprecipitation; CQ: chloroquine; DDX10: DEAD-box helicase 10; E: envelope; EGFP: enhanced green fluorescent protein; hpi: hours post infection; hpt: hours post transfection; IFA: indirect immunofluorescence assay; IFN-I: type I IFN; IFNB/IFN-ß: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; KO: knockout; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; mAb: monoclonal antibody; MOI: multiplicity of infection; NBR1: NBR1 autophagy cargo receptor; NFKB/NF-κB: nuclear factor kappa B; OPTN: optineurin; ORF: open reading frame; PRRSV: porcine reproductive and respiratory syndrome virus; SeV: sendai virus; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: 50% tissue culture infective dose; WT: wild type.