Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV-2 infection. We profiled MIS-C, adult COVID-19, and healthy pediatric and adult individuals using single-cell RNA sequencing, flow cytometry, antigen receptor repertoire analysis, and unbiased serum proteomics, which collectively identified a signature in MIS-C patients that correlated with disease severity. Despite having no evidence of active infection, MIS-C patients had elevated S100A-family alarmins and decreased antigen presentation signatures, indicative of myeloid dysfunction. MIS-C patients showed elevated expression of cytotoxicity genes in NK and CD8+ T cells and expansion of specific IgG-expressing plasmablasts. Clinically severe MIS-C patients displayed skewed memory T cell TCR repertoires and autoimmunity characterized by endothelium-reactive IgG. The alarmin, cytotoxicity, TCR repertoire, and plasmablast signatures we defined have potential for application in the clinic to better diagnose and potentially predict disease severity early in the course of MIS-C.

ArhGEF12 activates Rap1A and not RhoA in human dermal microvascular endothelial cells to reduce tumor necrosis factor-induced leak.

Overwhelming inflammation in the setting of acute critical illness induces capillary leak resulting in hypovolemia, edema, tissue dysoxia, organ failure and even death. The tight junction (TJ)-dependent capillary barrier is regulated by small GTPases, but the specific regulatory molecules most active in this vascular segment under such circumstances are not well described. We set out to identify GTPase regulatory molecules specific to endothelial cells (EC) that form TJs. Transcriptional profiling of confluent monolayers of TJ-forming human dermal microvascular ECs (HDMECs) and adherens junction only forming-human umbilical vein EC (HUVECs) demonstrate ARHGEF12 is basally expressed at higher levels and is only downregulated in HDMECs by junction-disrupting tumor necrosis factor (TNF). HDMECs depleted of ArhGEF12 by siRNA demonstrate a significantly exacerbated TNF-induced decrease in trans-endothelial electrical resistance and disruption of TJ continuous staining. ArhGEF12 is established as a RhoA-GEF in HUVECs and its knock down would be expected to reduce RhoA activity and barrier disruption. Pulldown of active GEFs from HDMECs depleted of ArhGEF12 and treated with TNF show decreased GTP-bound Rap1A after four hours but increased GTP-bound RhoA after 12 h. In cell-free assays, ArhGEF12 immunoprecipitated from HDMECs is able to activate both Rap1A and RhoA, but not act on Rap2A-C, RhoB-C, or even Rap1B which shares 95% sequence identity with Rap1A. We conclude that in TJ-forming HDMECs, ArhGEF12 selectively activates Rap1A to limit capillary barrier disruption in a mechanism independent of cAMP-mediated Epac1 activation.

Highly potent anti-inflammatory, analgesic and antioxidant activities of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thiones.

Four series of tetrahydro-2H-1,3,5-thiadiazine-2-thiones (series A and B including two novel enantiopure isomers), tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series C) and N-3 ester derivatives of tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series D) were synthesized and evaluated for their anti-inflammatory, analgesic and anti-oxidant activities. These THTT analogues specially series D were first time examined for their in vitro anti-inflammatory, in vivo analgesic and anti-oxidant activities. Among them lipophilic compounds (series B and D) were found to be highly active for anti-inflammatory evaluation with IC50 values between 5.1-16.9 and 4.1-32.4 µM, respectively when compared with the standard drug ibuprofen IC50 = 11.2 µM. The structure-activity relationship exposed the importance of lipophilic substituents especially ester and n-propyl group for inhibition of inflammation. The molecular docking studies demonstrated that all the active analogues of THTT have notable binding relations with Arg120 of the active sites of COX-1 enzyme either through CS moiety of the THTT nucleus or with COO attached at N-3 of THTT nucleus. In vivo analgesic activity of the selected THTT compounds 14, 17, 18, 19 (series B) and 28 (series D) were also carried out by acetic acid-induced writhing procedure. The compound 28 showed significant anti-nociceptive/analgesic activity at the oral dose of 5 mg/kg body weight with the percent protection (32.05 %) when compared with standard indomethacin at 10 mg/kg (48.83 %). Additionally, these compounds demonstrated the moderate level of antioxidant potential with IC50 values in the range of 60.9 to 93.6 µM (standard butylated hyroxyanisole; IC50 = 44.2 µM). These results indicated that this class of heterocyclic compounds may be a template specially to design better anti-inflammatory and analgesic agents.

Tumor necrosis factor-induced ArhGEF10 selectively activates RhoB contributing to human microvascular endothelial cell tight junction disruption.

Capillary endothelial cells (ECs) maintain a semi-permeable barrier between the blood and tissue by forming inter-EC tight junctions (TJs), regulating selective transport of fluid and solutes. Overwhelming inflammation, as occurs in sepsis, disrupts these TJs, leading to leakage of fluid, proteins, and small molecules into the tissues. Mechanistically, disruption of capillary barrier function is mediated by small Rho-GTPases, such as RhoA, -B, and -C, which are activated by guanine nucleotide exchange factors (GEFs) and disrupted by GTPase-activating factors (GAPs). We previously reported that a mutation in a specific RhoB GAP (p190BRhoGAP) underlays a hereditary capillary leak syndrome. Tumor necrosis factor (TNF) treatment disrupts TJs in cultured human microvascular ECs, a model of capillary leak. This response requires new gene transcription and involves increased RhoB activation. However, the specific GEF that activates RhoB in capillary ECs remains unknown. Transcriptional profiling of cultured tight junction-forming human dermal microvascular endothelial cells (HDMECs) revealed that 17 GEFs were significantly induced by TNF. The function of each candidate GEF was assessed by short interfering RNA depletion and trans-endothelial electrical resistance screening. Knockown of ArhGEF10 reduced the TNF-induced loss of barrier which was phenocopied by RhoB or dual ArhGEF10/RhoB knockdown. ArhGEF10 knockdown also reduced the extent of TNF-induced RhoB activation and disruption at tight junctions. In a cell-free assay, immunoisolated ArhGEF10 selectively catalyzed nucleotide exchange to activate RhoB, but not RhoA or RhoC. We conclude ArhGEF10 is a TNF-induced RhoB-selective GEF that mediates TJ disruption and barrier loss in human capillary endothelial cells.

Ponseti Technique For Management Of Congenital Idiopathic Club Foot.

BACKGROUND: Clubfoot or congenital talipes equinovarus, is a congenital deformity of the foot. It consists of cavus, adduction, varus and equinus. This is due to medial displacement of navicular and calcaneus around the talus. Talus is in equinus. Medial deviation of the head and neck of talus is due to force of calcaneus on talus. METHODS: This descriptive case series study was conducted at Orthopaedic unit, Ayub Teaching Hospital, Abbottabad from 1st August 2015 to 31st January 2016 to determine the frequency of idiopathic clubfoot correction, by using the Ponseti method. A total of 177, unilateral and bilateral clubfeet, from both genders were studied. Patients between age of 2 weeks to 2 years were included in the study. Basic pirani score six (06) who were previously untreated were included in the study. Syndromic patients, previously treated and patients with associated neuro-mascular disorders were excluded from the study. Patients who were corrected with serial castings, were put in foot abduction brace. Those who needed some sort of surgery underwent surgery. All the data was collected in the proforma and analysed by SPSS version 16.00. RESULTS: A total of 177 clubfeet were included in the study. Mean age of the patients was 10.28±7.45 ranging from 2 weeks 2 years. There were 93 (52.5%) male and 84 (43.5%) female out of total 177 patients. Of these 20 patients were corrected with serial casting only while 150 patients underwent percutaneous tenotomy, which is a minor procedure and done on out -patient department basis. After correction, the feet were put in 70 degree of abduction in abduction brace. Only 7 patients required some sort of surgery, more than tenotomy. CONCLUSIONS: Ponseti is very effective, economical and non-invasive way of treating congenital idiopathic clubfoot. Only resistant cases may need some sort of extensive surgery.

Surgical Site Infection In Orthopaedic Implants And Its Common Bacteria With Their Sensitivities To Antibiotics, In Open Reduction Internal Fixation.

BACKGROUND: Surgical site infection in orthopaedic implants is a major problem, causing long hospital stay, cost to the patient and is a burden on health care facilities. It increases rate of nonunion, osteomyelitis, implant failure, sepsis, multiorgan dysfunction and even death. Surgical site infection is defined as pain, erythema, swelling and discharge from wound site. Surgical site infection in orthopaedic implants is more challenging to the treating orthopaedic surgeon as the causative organism is protected by a biofilm over the implant's surface. Antibiotics cannot cross this film to reach the bacteria's, causing infection. METHODS: This descriptive case series study includes 132 patients of both genders with ages between 13-60 years conducted at Orthopaedic Unit, Ayub Medical College, Abbottabad from 1st October 2015 to 31st March 2016. Patients with close fractures of long bones were included in the study to determine the frequency of surgical site infection in orthopaedic implants and the type of bacteria involved and their sensitivity to various antibiotics. All implants were of stainless steel. The implants used were Dynamic hip screws, Dynamic compression screws, plates, k-wires, Interlocking nails, SIGN nails, Austin Moore prosthesis and tension band wires. Pre-op and post-op antibiotics used were combination of Sulbactum and Cefoperazone which was given 1 hour before surgery and continued for 72 hours after surgery. Patients were followed up to 4 weeks. Pus was taken on culture stick, from those who developed infection. Results were entered in the pro forma. RESULTS: A total of 132 patients of long bone fractures, who were treated with open reduction and internal fixation, were studied. Only 7 patients developed infection. Staphylococcus Aureus was isolated from all 7 patients. Staphylococcus aureus was sensitive to Linezolid, Fusidic Acid, and vancomycin. Cotrimoxazole, tetracycline, Gentamycin and Clindamycin were partially effective. CONCLUSIONS: Surgical Site Infection is common in orthopaedic implants, occurring in 5.30% cases. Staphylococcus aureus is the common bacteria, causing it.

OUTCOMES IN CLOSED REAMED INTERLOCKING NAIL IN FRACTURES OF SHAFT OF FEMUR.

BACKGROUND: Femoral shaft fracture is one of the common fractures seen in accident and emergency department of our hospital. Violent forces are required to break this and strongest of human bones. There are various treatment modalities for femoral shaft fractures in adults like traction, brace, platting, intramedullary nail (IMN), external fixators and inter locking nails. The study was done with an objective to evaluate the results of closed reamed interlocking nail in fractures of shaft of femur. METHODS: A prospective study of 114 cases of femoral shaft fractures was carried out at orthopaedic unit of Ayub Teaching Hospital Abbottabad during 1 year. All these cases were treated with statically locked nails under spinal or general anaesthesia. These cases were followed up for up to one year and Results of the interlocking nail were observed in terms of union and complications. RESULTS: Out of 114 patients, 95 underwent union in 90-150 days with a mean of 110.68 days. Ten patients had dynamization within six weeks because of obvious fracture gap in radiograph. There were 3 patients who had non-union, and 6 patients had delayed union which was treated with dynamization. CONCLUSION: Close reamed interlocking intramedullary nail in femoral shaft fractures is the treatment of choice. Patient rehabilitation is early, hospitalization is short, and fracture healing response is good.

EARLY RESPONSE OF LOCAL STEROID INJECTION VERSUS MINI INCISION TECHNIQUE IN TREATMENT OF CARPAL TUNNEL SYNDROME.

BACKGROUND: Carpal tunnel syndrome (CTS) is one of the commonest peripheral neuropathies which effects mainly middle aged women. Different techniques are being tried to decrease the postoperative pain in patients operated for CTS. The objective of this study was to compare effectiveness of local injection of steroid and mini incision technique in the treatment of carpal tunnel syndrome. METHODS: This randomized control trial was conducted at department of Orthopedics and department of Neurosurgery, Ayub Teaching Hospital, Abbottabad from Aug 2011 to Feb 2013. A total of 116 patients of CTS were randomly allocated to either of the two groups.58 Patient in Group A were subjected to local steroid injection and the same number of patient in Group B underwent mini incision technique. All patients of were advised to report to the OPD after one month to determine intervention effectiveness in terms of improvement in at least one grade of pain. RESULTS: In this study mean age of the patients was 32.8 +/- 5.1 years. Female gender was in dominance with 99 (86.3%) cases. In this study we compared the effectiveness of local steroid injection and mini incision technique in the treatment of carpel tunnel syndrome. We found out that the steroid injection was effective in 69.0% cases while mini incision technique was effective in 56.9% cases. The difference being statistically insignificant with a p-value of 0.17. CONCLUSION: The difference in pain after 1 month of the intervention was not statistically significant.

Rare craniofacial clefts: Surgical management protocols.

BACKGROUND: Standardization of surgical protocols is an evolving issue owing to the low incidence of rare craniofacial clefts. In this article, we present our surgical management technique for repair of rare craniofacial clefts and evaluate the postoperative results. METHODS: This study was conducted from 2013 to 2022 and included patients who presented with craniofacial clefts. The results were assessed based on parents' satisfaction and objective evaluations by two independent observers. RESULTS: A total of 3679 patients presented with cleft anomalies; of these, 61 patients with 89 rare craniofacial clefts were observed with a prevalence of 2.42/100. The male to female ratio was 1:1.35. Craniofacial cleft "4" and "5" were the most common, with 17 (19.1%) and 16 (17.98%) patients, respectively. Multiple craniofacial clefts were observed in 37.7% of the patients. Associated craniofacial anomalies were found in 39.34% of the patients. The parents of 71.6% of the patients were very satisfied with the results. Based on the scores of two independent observers, 70.27% of the patients showed good results. CONCLUSION: The rare nature of craniofacial clefts and involvement of various structures make the standardization of surgical procedures very challenging. Our experience with these clefts will help new surgeons both in didactics and in technical aspects of patient management. KEY POINTS: 1. We share our experience with rare craniofacial clefts. 2. Each cleft presents with its own unique reconstructive challenges. The literature describes many techniques for each type of cleft, all with multiple permutations. We present a simplified technique that has worked for us over the years for all Tessier clefts.

Unveiling cutting-edge developments: architectures and nanostructured materials for application in optoelectronic artificial synapses.

One possible result of low-level characteristics in the traditional von Neumann formulation system is brain-inspired photonics technology based on human brain idea. Optoelectronic neural devices, which are accustomed to imitating the sensory role of biological synapses by adjusting connection measures, can be used to fabricate highly reliable neurologically calculating devices. In this case, nanosized materials and device designs are attracting attention since they provide numerous potential benefits in terms of limited cool contact, rapid transfer fluidity, and the capture of photocarriers. In addition, the combination of classic nanosized photodetectors with recently generated digital synapses offers promising results in a variety of practical applications, such as data processing and computation. Herein, we present the progress in constructing improved optoelectronic synaptic devices that rely on nanomaterials, for example, 0-dimensional (quantum dots), 1-dimensional, and 2-dimensional composites, besides the continuously developing mixed heterostructures. Furthermore, the challenges and potential prospects linked with this field of study are discussed in this paper.

Mulliken's Bilateral Cleft Lip Repair: Early Outcome Analysis.

OBJECTIVE: To determine the early surgical outcome of Mulliken's repair technique for bilateral cleft lip. STUDY DESIGN: Descriptive cross-sectional study. Place and Duration of the study: Burns and Plastic Surgery Centre, Hayatabad Medical Complex, Peshawar, Pakistan, from January 2020 to December 2021. METHODOLOGY: This study included 51 patients with bilateral cleft lip deformity. Patients were evaluated preoperatively to exclude any associated congenital anomalies or comorbidities. Then the patients were classified into mild, moderate, severe, and asymmetrical cases. Outcomes were determined immediately and one week postoperatively, as good (score 16-20), fair (score 11-15), and bad (0-10) on the basis of anthropometric measurements on outcome evaluation criteria (OEC). RESULTS: Preoperatively mild, moderate, and severe bilateral cleft lips were observed in 18 (35.3%), 6 (11.85%), and 15 (29.4%), respectively, while 10 (19.6%) were bilateral asymmetrical cleft lips. The postoperative outcome score ranged from 16 to 20 (mean 19.2+1.03) which falls in the good outcome range. Nasal symmetry was good in 64.7% (n=33) cases while 31.4% (n=16) patients had satisfactory scores. CONCLUSION: Although Mulliken's repair is by far the most prevalent type of repair for bilateral cleft lip patients, the results can vary markedly. The early outcome evaluation criteria is an objective tool to measure the outcomes. KEY WORDS: Cleft lip, Bilateral cleft lip, Mulliken, Mulliken's repair, Day care surgery, Outcome.

A memory effect model to predict COVID-19: analysis and simulation.

On 19 September 2020, the Centers for Disease Control and Prevention (CDC) recommended that asymptomatic individuals, those who have close contact with infected person, be tested. Also, American society for biological clinical comments on testing of asymptomatic individuals. So, we proposed a new mathematical model for evaluating the population-level impact of contact rates (social-distancing) and the rate at which asymptomatic people are hospitalized (isolated) following testing due to close contact with documented infected people. The model is a deterministic system of nonlinear differential equations that is fitted and parameterized by least square curve fitting using COVID-19 pandemic data of Pakistan from 1 October 2020 to 30 April 2021. The fractional derivative is used to understand the biological process with crossover behavior and memory effect. The reproduction number and conditions for asymptotic stability are derived diligently. The most common non-integer Caputo derivative is used for deeper analysis and transmission dynamics of COVID-19 infection. The fractional-order Adams-Bashforth method is used for the solution of the model. In light of the dynamics of the COVID-19 outbreak in Pakistan, non-pharmaceutical interventions (NPIs) in terms of social distancing and isolation are being investigated. The reduction in the baseline value of contact rates and enhancement in hospitalization rate of symptomatic can lead the elimination of the pandemic.

Structural and Functional Characterization of Novel Phosphotyrosine Phosphatase Protein from Drosophila melanogaster (Pupal Retina).

A novel pair of protein tyrosine phosphatases in Drosophila melanogaster (pupal retina) has been identified. Phosphotyrosyl protein phosphatases (PTPs) are structurally diverse enzymes increasingly recognized as having a fundamental role in cellular processes including effects on metabolism, cell proliferation, and differentiation. This study presents identification of novel sequences of PTPs and their comparative homology modeling from Drosophila melanogaster (Dr-PTPs) and complexation with the potent inhibitor HEPES. The 3D structure was predicted based on sequence homology with bovine heart low molecular weight PTPs (Bh-PTPs). The sequence homologies are approximately 50% identical to each other and to low molecular weight protein tyrosine phosphatases (PTPs) in other species. Comparison of the 3D structures of Bh-PTPs and Dr-PTPs (primo-2) reveals a remarkable similarity having a four stranded central parallel ß sheet with flanking α helices on both sides, showing two right handed ß-α-ß motifs. The inhibitor shows similar binding features as seen in other PTPs. The study also highlights the key catalytic residues important for target recognition and PTPs' activation. The structure guided studies of both proteins clearly reveal a common mechanism of action and inhibitor binding at the active site and will be expected to contribute toward the basic understanding of functional association of this enzyme with other molecules.

MicroRNA-1 protects the endothelium in acute lung injury.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), cause severe endothelial dysfunction in the lung, and vascular endothelial growth factor (VEGF) is elevated in ARDS. We found that the levels of a VEGF-regulated microRNA, microRNA-1 (miR-1), were reduced in the lung endothelium after acute injury. Pulmonary endothelial cell-specific (EC-specific) overexpression of miR-1 protected the lung against cell death and barrier dysfunction in both murine and human models and increased the survival of mice after pneumonia-induced ALI. miR-1 had an intrinsic protective effect in pulmonary and other types of ECs; it inhibited apoptosis and necroptosis pathways and decreased capillary leak by protecting adherens and tight junctions. Comparative gene expression analysis and RISC recruitment assays identified miR-1 targets in the context of injury, including phosphodiesterase 5A (PDE5A), angiopoietin-2 (ANGPT2), CNKSR family member 3 (CNKSR3), and TNF-α-induced protein 2 (TNFAIP2). We validated miR-1-mediated regulation of ANGPT2 in both mouse and human ECs and found that in a 119-patient pneumonia cohort, miR-1 correlated inversely with ANGPT2. These findings illustrate a previously unknown role of miR-1 as a cytoprotective orchestrator of endothelial responses to acute injury with prognostic and therapeutic potential.

Threshold switching in nickel-doped zinc oxide based memristor for artificial sensory applications.

Electronic devices featuring biomimetic behaviour as electronic synapses and neurons have motivated the emergence of a new era in information and humanoid robotics technologies. In the human body, a nociceptor is a unique sensory neuron receptor that is capable of detecting harmful signals, leading to the central nervous system initiating a motor response. Herein, a nickel-doped zinc oxide (NZO)/Au based memristor is fabricated for the first time and characterized for artificial nociceptor application. For this, the introduction of a nickel-doped zinc oxide (NZO) layer between P++-Si and Au electrodes is used to eliminate the surface effects of the NZO layer, resulting in improved volatile threshold switching performance. Depending on the intensity, duration, and repetition rate of the external stimuli, this newly created memristor exhibits various critical nociceptive functions, including threshold, relaxation, allodynia, and hyperalgesia. The electron trapping/detrapping to/from the traps in the NZO layer is responsible for these nociceptive properties. This kind of NZO-based device produces a multifunctional nociceptor performance that is essential for applications in artificial intelligence systems, such as neural integrated devices with nanometer-sized features.

Heparin-Assisted Amyloidogenesis Uncovered through Molecular Dynamics Simulations.

Glycosaminoglycans (GAGs), in particular, heparan sulfate and heparin, are found colocalized with Aß amyloid. They have been shown to enhance fibril formation, suggesting a possible pathological connection. We have investigated heparin's assembly of the KLVFFA peptide fragment using molecular dynamics simulation, to gain a molecular-level mechanistic understanding of how GAGs enhance fibril formation. The simulations reveal an exquisite process wherein heparin accelerates peptide assembly by first "gathering" the peptide molecules and then assembling them. Heparin does not act as a mere template but is tightly coupled to the peptides, yielding a composite protofilament structure. The strong intermolecular interactions suggest composite formation to be a general feature of heparin's interaction with peptides. Heparin's chain flexibility is found to be essential to its fibril promotion activity, and the need for optimal heparin chain length and concentration has been rationalized. These insights yield design rules (flexibility; chain-length) and protocol guidance (heparin:peptide molar ratio) for developing effective heparin mimetics and other functional GAGs.

New records of Amblyomma gervaisi from Pakistan, with detection of a reptile-associated Borrelia sp.

Ticks are hematophagous ectoparasites of terrestrial and semi-aquatic vertebrates that may transmit microorganisms to their hosts. Spirochetes of the genus Borrelia are common in ticks and an incipient group has been identified in association with reptiles and their tick parasites. To overcome the knowledge deficit, this study aimed to morphologically and molecularly identify ticks infesting wild lizards and to molecularly assess Borrelia spp. associated with these ticks in Pakistan. For this purpose, free-ranging monitor lizards (Varanus bengalensis) from Khyber Pakhtunkhwa province, Pakistan, were examined for tick infestations. A total of 776 ticks were collected from 36/63 lizards, resulting in a prevalence of 57% (95% CI 44.7-69.3%), overall mean intensity of 21.5 (95% CI 18.9-24.1) ticks per infested lizard, and overall mean abundance of 12.3 (95% CI 9.25-15.4) ticks per examined lizard. All ticks were morphologically identified as Amblyomma gervaisi. The morphological identification of the ticks was molecularly confirmed through sequencing fragments of the mitochondrial 16S rRNA gene. In addition, a fragment of nuclear second internal transcribed spacer (ITS2) was generated for the first time for A. gervaisi. Phylogenetic analysis inferred from tick 16S rRNA gene partial sequences predicted a close evolutionary relationship of the collected A. gervaisi ticks with conspecific sequences from India, which shared 94.5% identity. Through two PCR assays targeting fragments of the borrelial genes, 16S rRNA and flaB, 19 (18%) out of 108 ticks yielded borrelial DNA. Phylogenetic analyses inferred from DNA sequences of the two borrelial genes revealed that the Borrelia sp. from A. gervaisi detected in this study belonged to the reptile-associated Borrelia group (REP). This is the first molecular report of ticks infesting monitor lizards and associated Borrelia sp. in Pakistan. The preliminary phylogenetic analyses of A. gervaisi may assist in understanding the molecular epidemiology of Amblyomma spp.

Molecular characterization of Mycobacterium tuberculosis through MPT64 gene polymorphism using next-generation sequencing technology.

Aim: To characterize and analyze polymorphism of the MPT64 gene and evaluate AgMPT64-based immunochromatographic assay (ICA) specificity associated with polymorphism. Materials & methods: A total of 1449 suspected samples were tested for tuberculosis (TB), and the MPT64/rv1980c gene was sequenced using next-generation sequencing for polymorphism analysis. Results: Of the TB-positive individuals, 200 (13.80%), 186 (12.84%) and 129 (8.90%) were positive using the liquid culture, GeneXpert and fluorescence microscopy assays, respectively. Liquid culture medium-based samples were confirmed using ICA, in which 193 (96.5%) were positive while seven (3.5%) were negative. Out of 14 sequenced samples, seven were positive and seven negative; 13 were identical to the reference and just one (ICA positive) showed a C477A point mutation (F159L). Conclusion: The results indicate that AgMPT64 can be considered as a potent vaccine candidate.

Room temperature dilute magnetic semiconductor response in (Gd, Co) co-doped ZnO for efficient spintronics applications.

The co-precipitation approach was utilized to experimentally synthesize ZnO, Zn0.96Gd0.04O and Zn0.96-x Gd0.04Co x O (Co = 0, 0.01, 0.03, 0.04) diluted magnetic semiconductor nanotubes. The influence of gadolinium and cobalt doping on the microstructure, morphology, and optical characteristics of ZnO was investigated, and the Gd doping and Co co-doping of the host ZnO was verified by XRD and EDX. The structural investigation revealed that the addition of gadolinium and cobalt to ZnO reduced crystallinity while maintaining the preferred orientation. The SEM study uncovered that the gadolinium and cobalt dopants did not affect the morphology of the produced nanotubes, which is further confirmed through TEM. In the UV-vis spectra, no defect-related absorption peaks were found. By raising the co-doping content, the crystalline phase of the doped samples was enhanced. It was discovered that the dielectric response and the a.c. electrical conductivity display a significant dependent relationship. With the decreasing frequency and increasing Co co-dopant concentration, the ε r and ε'' values decreased. It was also discovered that the ε r, ε'', and a.c. electrical conductivity increased when doping was present. Above room temperature, co-doped ZnO nanotubes exhibited ferromagnetic properties. The ferromagnetic behaviour increased as Gd (0.03) doping increased. Increasing the Co content decreased the ferromagnetic behaviour. It was observed that Zn0.96-x Gd0.04Co x O (x = 0.03) nanotubes exhibit superior electrical conductivity, magnetic and dielectric characteristics compared to pure ZnO. This high ferromagnetism is typically a result of a magnetic semiconductor that has been diluted. In addition, these nanoparticles are utilized to design spintronic-based applications in the form of thin-films.

Enhancing the physical properties and photocatalytic activity of TiO2 nanoparticles via cobalt doping.

Cobalt-doped TiO2-based diluted magnetic semiconductors were successfully synthesized using a co-precipitation method. The X-ray diffraction study of all the samples showed good crystallinity, matching the standard tetragonal anatase phase. The X-ray diffraction peaks of the cobalt-doped sample slightly shifted towards a lower angle showing the decrease in particle size and distortion in the unit cell due to cobalt incorporation in the lattice of TiO2. Transmission electron microscopy showed the spherical morphology of the TiO2 nanoparticles, which decreased with Co-doping. The optical characteristics and band gap investigation revealed that defects and oxygen vacancies resulted in lower band gap energy and maximum absorption in the visible region. Dielectric measurements showed enhancement in the dielectric constant and AC conductivity, while the dielectric loss decreased. The enhancement in the dielectric properties was attributed to interfacial polarization and charge carrier hopping between Co and Ti ions. The magnetic properties displayed that pure TiO2 was diamagnetic, while Co-doped TiO2 showed a ferromagnetic response at 300 K. The visible light-driven photocatalytic activity showed an improvement for Co-doped TiO2. Our results demonstrate that Co-doping can be used to tune the physical properties and photocatalytic activity of TiO2 for possible spin-based electronics, optoelectronics, and photo-degradation applications.