Room Temperature Relaxometry of Single Nitrogen Vacancy Centers in Proximity to α-RuCl3 Nanoflakes.

Nitrogen vacancy (NV) center-based magnetometry has been proven to be a versatile sensor for various classes of magnetic materials in broad temperature and frequency ranges. Here, we use the longitudinal relaxation time T1 of single NV centers to investigate the spin dynamics of nanometer-thin flakes of α-RuCl3 at room temperature. We observe a significant reduction in the T1 in the presence of α-RuCl3 in the proximity of NVs, which we attribute to paramagnetic spin noise confined in the 2D hexagonal planes. Furthermore, the T1 time exhibits a monotonic increase with an applied magnetic field. We associate this trend with the alteration of the spin and charge noise in α-RuCl3 under an external magnetic field. These findings suggest that the influence of the spin dynamics of α-RuCl3 on the T1 of the NV center can be used to gain information about the material itself and the technique to be used on other 2D materials.

In vitro and Bioimaging Studies of Mesoporous Silica Nanocomposites Encapsulated Iron-oxide and Loaded Doxorubicin Drug (DOX/IO@Silica) as Magnetically Guided Drug Delivery System.

BACKGROUND: In recent years, the delivery of drugs by nanocomposites has emerged as an exciting field of research for bio-imaging tools and targeted cancer treatment. The large surface area and porous volume of mesoporous silica nanocomposites (MSN's) have gained a lot of interest for their application in the delivery of drugs and the magnetic properties of iron oxide (IO) nanocomposites play a key role in the targeted delivery system. METHODS: In this study, mesoporous silica encapsulated IO nanocomposites loaded with doxorubicin (DOX) were synthesized for the magnetically guided delivery of anticancer drugs. The synthesis of IO nanocomposites was done through the precipitation method, and then silica encapsulation and drug loading were done by the StÖber method. RESULTS: The magnetically driven delivery of the drug is produced by the encapsulation of magnetically active IO in the mesoporous silica shell. The controlled release of DOX is possible because of the MSN's. TEM images show that the nanocomposites have a spherical morphology and average diameter in the range of 120 nm. Power-XRD data confirm the crystalline nature of nanocomposites. The strong absorption peak was observed in UV-Visible spectroscopy at 490 nm and quenching in fluorescence spectra confirms the encapsulation of DOX in the mesoporous silica shell. VSM data showed the magnetic nature of nanocomposites, with large magnetic susceptibility (74.88 emu/g). The use of DOX/IO@Silica nanocomposites as a sustainable drug release and targeted drug delivery vehicle has been reported here. The pH dependent release of DOX was studied and significant release was observed at lower pH. In-vitro cell viability assay and fluorescence imaging assay have demonstrated that these nanocomposites show significant dose-dependent toxicity to cancer cells in the presence of a magnetic field. CONCLUSION: In-vitro studies via the MTT assay showed that these synthesized nanocomposites in culture are non-toxic to healthy cells compared to DOX-induced cytotoxicity due its controlled release and can be further strengthened by magnetic guidance. Therefore, due to its optical properties and potential for guided delivery of drug to the targeted site, these nanocomposites are ideal as an anticancer agent and bio-imaging prob.

Biosynthesis of anticancer phytochemical compounds and their chemistry.

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption remain more significant obstacles in clinical trials. Therefore, drug combinations of new phytochemical compounds, phytonanomedicine, semi-synthetic, and synthetic analogs should be considered to supplement the existing cancer therapies. It is also crucial to consider different strategies for increased production of phytochemical bioactive substances. The primary goal of this review is to highlight several bioactive anticancer phytochemical compounds found in plants, preclinical research, their synthetic and semi-synthetic analogs, and clinical trials. Additionally, biotechnological and metabolic engineering strategies are explored to enhance the production of bioactive phytochemical compounds. Ligands and their interactions with their putative targets are also explored through molecular docking studies. Therefore, emphasis is given to gathering comprehensive data regarding modern biotechnology, metabolic engineering, molecular biology, and in silico tools.

Use of Intraoperative C-Arm Fluoroscopy in Open Reduction and Internal Fixation of Mandibular Condyle Fracture - A Case Report.

The Rationale: Condyle fractures are a common type of mandibular fracture that can result in malocclusion. Open reduction and internal fixation (ORIF) in condylar fracture is considered as the most acceptable treatment modality. Patient Concerns: The patient complained of pain and difficulty in the jaw while chewing. Diagnosis: An orthopantomogram and reverse Towne's view can lead to diagnosis of the condylar fracture. Treatment: Open reduction and internal fixation using intraoperative real-time visualisation of subcondylar fracture reduction utilising the C-arm fluoroscopic approach were used to allow for adequate anatomical repositioning and fast restoration of function to meet the patient's concerns. Outcomes: We were able to achieve correct reduction of the fracture fragments with restoration of function and occlusion. Take-away Lessons: When this procedure is used to treat condylar fractures, surgeons can get a better view of the fracture segments while eliminating the need for postoperative intermaxillary fixation and also reduces the complications from inappropriate reduction and fixation.

Highly Selective and Sensitive Ratiometric Detection of Sn2+ Ions Using NIR-Excited Rhodamine-B-Linked Upconversion Nanophosphors.

Detection of Sn2+ ions in environmental and biological samples is essential owing to the toxicological risk posed by excess use tin worldwide. Herein, we have designed a nanoprobe involving upconversion nanophosphors linked with a rhodamine-based fluorophore, which is selectively sensitive to the presence of Sn2+ ions. Upon excitation with near-infrared (NIR) light, the green emission of the nanophosphor is reabsorbed by the fluorophore with an efficiency that varies directly with the concentration of the Sn2+ ions. We have explored this NIR-excited fluorescence resonance energy transfer (FRET) process for the quantitative and ratiometric detection of Sn2+ ions in an aqueous phase. We have observed an excellent linear correlation between the ratiometric emission signal variation and the Sn2+ ion concentration in the lower micromolar range. The detection limit of Sn2+ ions observed using our FRET-based nanoprobe is about 10 times lower than that observed using other colorimetric or fluorescence-based techniques. Due to the minimal autofluorescence and great penetration depth of NIR light, this method is ideally suited for the selective and ultrasensitive detection of Sn2+ ions in complex biological or environmental samples.

Anomalous dielectric response in the triple perovskite ruthenate Ba3BiRu2O9.

We have investigated the magnetic, dielectric and thermal properties of theSRu= 1 magnetic dimer Ba3BiRu2O9, which is known to exhibit a spin-gap opening in conjunction with a first-order magneto-elastic phase transition at ∼175 K. Above the spin-gap temperature, the temperature dependence dielectric constant shows a peak like feature with pronounced frequency dependence. The critical slowing down behavior of this frequency dispersion suggests that a ferroelectric relaxor like electrical glassy state exists above the spin-gap opening temperature regime. The extermination of frequency dispersion-right at the magneto-elastic phase transition, is suggestive of a strong coupling between the lattice and charge-spin degrees of freedom in this triple perovskite system.

Effect of Eu doping on the thermoluminescence of UV and gamma irradiated Mg2 B2 O5 nanophosphors.

This article presents the effect of europium (Eu) doping on the thermoluminescence (TL) of ultraviolet (UV-254 nm) and gamma irradiated triclinic Mg2 B2 O5 nanophosphors. The diffuse reflectance predicts slight decrease in band gap from 5.18 to 4.99 eV with increasing Eu (1%, 3%, and 5%) content in Mg2 B2 O5 . The TL glow curves of UV irradiated samples comprised of a main peak around 500 K with weak intensity peak/shoulders in low temperature region. Interestingly Eu (3%) doped Mg2 B2 O5 shows maximum TL intensity with suppression of low temperature shoulder peaks and almost linear UV dose dependent TL response. However, in the case of gamma irradiated Eu (1% and 3% doped) samples, TL glow curve comprises of a main peak around 425-445 K and closely lying peak around 500-515 K with relatively lesser intensity. In case of Eu (5%) doped samples, TL peak around 508 K starts dominating over peak around 425 K. TL of both UV and gamma irradiated samples showed the presence of various deep and shallow defect states within the bandgap of materials having different kinetic parameters, which were determined using TLanal software based on Kiti's general order equation. The present study shows that Eu doped Mg2 B2 O5 nanophosphors can be tuned for UV and gamma dosimetry.

Effect of natural radionuclide's in the environment along the Jwalamukhi thrust of Himachal Pradesh, North West Himalayas, India.

This research paper is devoted to measure the activity contents of natural radionuclide, like, radium (226Ra), thorium (232Th) and potassium (40K) in the soil gathered along the Jwalamukhi thrust of Himachal Pradesh, North Western Himalayas, India. NaI(Tl) Scintillator detector was utilized for the estimation of activity content. The activity concentration of 226Ra, 232Th and 40K for some of the soil samples have been observed to be above the global normal mean values. The outcomes acquired for indoor and outdoor effective dosage are well below the normal international and national proposed results. The determined values of external hazard (Hex) for studied locations are less than unity, therefore; samples assembled from these regions are safe from a health hazard point of view and can be utilized as a construction purposes without producing any radio-logical hazard to human beings. The average estimations of radium equivalent activity were found to be within the limits suggested by Organization for Economic Cooperation and Development (OECD). Radon (222Rn) and thoron (220Rn) exhalation rates have also been calculated and discussed.

Use of Foley's catheter as a tourniquet for the management of vascular lesion of lip in Mowat-Wilson syndrome.

BACKGROUND: Vascular malformation of lower lip is a very rare anomaly. The lesion leads to facial asymmetry, difficulty in speech and eating and drooling of saliva. Treatment goals include symmetrical reconstruction of the lip with minimal scarring, provide adequate bulk for the reconstruction of vermillion, in toto removal of the lesion and prevent recurrence. The most common complication during surgical removal of these lesions includes blood loss and profuse bleeding which leads to poor visibility, increased operation time and postoperative requirement of blood transfusion. Therefore, the use of sclerosing agent is recommended before surgical removal. This may help in decreasing bleeding during surgery but not in all cases. CASE REPORT: Here, we report the use of Foley's catheter for the management of a high flow lesion of lower lip in a 12-year-old patient diagnosed with Mowat-Wilson syndrome. This technique helped in providing bloodless field which lead to minimal blood loss and good visibility intraoperatively.

Efficacy of two siddha polyherbal decoctions, Nilavembu Kudineer and Kaba Sura Kudineer, along with standard allopathy treatment in the management of mild to moderate symptomatic COVID-19 patients-a double-blind, placebo-controlled, clinical trial.

BACKGROUND AND AIM: Globally, the ongoing pursuit in exploring an effective drug to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus has not met with significant success to date. Indian traditional medicines, especially polyherbal formulations like Nilavembu Kudineer (NVK) and Kaba Sura Kudineer (KSK) of the Siddha system of medicine, have been used as public health interventions for controlling viral epidemics like dengue and Chikungunya. These traditional therapies have been found safe, effective, and widely accepted. The current study evaluates the comparative efficacy of NVK and KSK as opposed to the placebo, in the management of mild to moderate COVID-19 disease. METHODS: The study was a double-blind, placebo-controlled comparative clinical trial, with the primary objective of determining the efficacy of KSK and NVK. Patients (n=125) diagnosed with mild to moderate COVID-19 symptoms were enrolled in the study over a period of 4 months (Aug 2020-Dec 2020). Participants were randomized into 3 arms; placebo-decaffeinated tea in Arm I, NVK in Arm II, and KSK in Arm III. Each arm received 60 ml of the respective treatment twice a day, post morning and evening meals, along with standard allopathy treatment for a maximum of 10 days. The main outcome measures of the study were the reduction in SARS-CoV-2 viral load, hospital stay, and time taken by the patients to become asymptomatic from symptomatic. Efficacy assessments included clinical symptoms (fever, cough, and breathlessness) each day and real-time reverse transcription-polymerase chain reaction (RT-PCR), liver function test (LFT), renal function test (RFT), and electrolytes and electrocardiogram (ECG) at baseline (day 0) and days 3, 6, and 10. Post-treatment, participants were followed up for 30 days via phone for adverse effects if any. Effects of drugs on inflammatory markers (IL6) at the end of treatment were also recorded. Adverse events (AE) were monitored throughout the study. RESULTS: The results revealed that when compared to patients in the placebo arm, those in NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and the time taken to become symptomatic from asymptomatic. Out of 125 COVID-19 patients recruited, 120 completed the study; two from the placebo group developed severe symptoms and were shifted to the intensive care unit (ICU) and three patients from Arms II and III withdrew from the study. The mean age of females (n=60) and males (n=60) enrolled was between 40.2 and 44.3 years, respectively. Results were more promising for all the patients in NVK and KSK arms as all enrolled participants (100%) under this group got discharged by day 6 as compared to only 42.5% (n=17) from the placebo group on that day. The hospital stay time for patients in Arm I was significantly longer (mean [SD]=8.4 [2.0] days) as compared to the Arms II and III (mean [SD]=4.7 [1.5] and 4.2 [1.5] days, respectively (Kruskal-Wallis test, P=0.0001). Patients in the three groups took a significantly different number of days to become asymptomatic. While Arm II and III patients took mean of 2.5 and 1.7 days, respectively, Arm I, patients took a mean of 4.2 days (Kruskal-Wallis test, P=0.0001). In all, two adverse events were recorded, one for vomiting and one for diarrhea lasting a day in Arm I and Arm II, respectively. The mean value of interleukin-6 (IL6) was significantly different in comparison to the placebo-decaffeinated tea arm (NVK=2.6 and KSK=2.2, placebo=4.0, P=0.02). The other blood biochemical parameters like C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer that were analyzed at the baseline and at the time of discharge from the hospital, were not significantly different in the three arms. CONCLUSION: NVK and KSK arms showed a statistically significant reduction in hospital stay time, reduction in viral load of SARS-CoV-2, and time taken for patients to become asymptomatic from symptomatic, when compared to the placebo (decaffeinated tea). The primary outcome measures of the KSK arm were significantly better than those in the NVK arm.

Structural, diffuse reflectance and luminescence study of t-Mg2B2O5 nanostructures.

We report here the structural, reflectance, photoluminescence and thermoluminescence study of t-Mg2B2O5 nanostructures synthesized using optimized combustion method relatively at much lower temperature. The rietveld refinement of X-ray diffraction data confirms single-phase triclinic crystal structure of Mg2B2O5 nanoparticles. The direct band gap determined using diffuse reflectance spectra (DRS) was 5.23 eV, which is contrary to earlier reports quoting Mg2B2O5 as indirect band gap material. To elucidate the nature of band gap in Mg2B2O5, we performed first principle calculations based on full potential linearized augmented plane-wave (FPLAPW) method, predicting the direct band gap of 5.10 eV in t-Mg2B2O5 which is in good agreement with our experimental results. The t-Mg2B2O5 nanoparticles were found to exhibit yellow-reddish photoluminescence peaking at 588 nm, attributed to various defects states. The combustion synthesized Mg2B2O5 nanocrystals exhibited ultraviolet (254 nm) responsive thermoluminescence (TL). TL glow curve of Mg2B2O5 comprises of one dominant peak around 417-428 K and less intense shoulder around 573-589 K which arouse possibility of various trapping sites or defects present in the sample. The TL analysis using general order Kitti's equations was performed to estimate the activation energies of trapping states. Owing to already well-known mechanical and thermal properties, the direct wide band gap nature and UV responsive thermoluminescence of combustion synthesized t-Mg2B2O5 nanostructures can pave way for its use in luminescence-based applications and UV dosimetry. As an additional application of Mg2B2O5, anti-biofilms activity of Mg2B2O5 nanoparticles using pseudomonas aeruginosa bacterial cells was also performed which revealed 91 ± 2.7% inhibition of biofilms formed by P. aeruginosa, respectively, at 100 µg/ml after 24 h of treatment.

Prevalence of Depression and Anxiety during the COVID-19 Pandemic among the Residents of an Urban Slum in North India.

Objectives This study aimed to estimate the prevalence of depression and anxiety, and assess the knowledge, practice, and concerns regarding coronavirus disease 2019 (COVID-19) among the residents of an urban slum in Chandigarh, India. Materials and Methods Participants were screened using Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales. Results The mean (standard deviation) age of 200 enrolled participants was 33 (13) years with 83% ( n = 166) being females. The prevalence of depression and anxiety was 3.5% (95% confidence interval [CI]: 0.95-6.05) and 2.5% (95% CI: 0.34-4.66), respectively. Of total, 46% ( n = 92) knew that COVID-19 can transmit through droplets and 30.5% ( n = 61) were concerned that they might get infected with disease. Half of the participants ( n = 100) believed that there was unnecessary worry regarding COVID-19 and 78% ( n = 156) covered mouth while coughing or sneezing. Conclusion To cope with this critical situation, it is necessary to strengthen the awareness programs targeting the mental health issues of the people.

Phosphorylation-induced changes in the PDZ domain of Dishevelled 3.

The PDZ domain of Dishevelled 3 protein belongs to a highly abundant protein recognition motif which typically binds short C-terminal peptides. The affinity of the PDZ towards the peptides could be fine-tuned by a variety of post-translation modifications including phosphorylation. However, how phosphorylations affect the PDZ structure and its interactions with ligands remains elusive. Combining molecular dynamics simulations, NMR titration, and biological experiments, we explored the role of previously reported phosphorylation sites and their mimetics in the Dishevelled PDZ domain. Our observations suggest three major roles for phosphorylations: (1) acting as an on/off PDZ binding switch, (2) allosterically affecting the binding groove, and (3) influencing the secondary binding site. Our simulations indicated that mimetics had similar but weaker effects, and the effects of distinct sites were non-additive. This study provides insight into the Dishevelled regulation by PDZ phosphorylation. Furthermore, the observed effects could be used to elucidate the regulation mechanisms in other PDZ domains.

Glandular Odontogenic Cyst of Anterior Maxilla - A Rare Case Report.

Rationale: Glandular odontogenic cyst (GOC) is a rare type of cyst of the jaws, which shares histological features with that of lateral periodontal cyst, botryoid cyst, radicular cyst with mucous metaplasia, or low-grade mucoepidermoid carcinoma, making it difficult to come to a definitive diagnosis. Not many cases of GOC have been reported in the literature. Patient Concerns: A 40-year-old male patient presented with pain in the upper right front tooth region. Mild extraoral swelling, obliterating the right nasolabial fold, was present. Tenderness on percussion was present in involved teeth. Diagnosis: On histopathological examination, GOC was confirmed featuring pseudostratified columnar cells with cilia, goblet cells, and mucous cells. Treatment: Complete enucleation of the cyst was done. Outcomes: No recurrence was noted on 1-year follow-up. Take-away Lessons: Due to high recurrence rate and aggressive nature of the cyst, it is important to plan proper management and long-term follow-up.

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.

BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

Assessment of contaminants in the northwestern Bay of Bengal.

The coastal sediments in the northern Bay of Bengal has undergone contamination due to the heavy metal contribution from rivers. To evaluate the status of contamination in the inner shelf region of the Bay of Bengal, a sediment core chronologically constrained using 210Pb dating technique from the northwest Bay of Bengal was investigated for several trace elements. To assess sediment quality, enrichment factor (EF), geo-accumulation index (Igeo), and Modified Nemerow Pollution Index (MPI) were derived. The influence on ecology by individual contaminants and combined contaminants was evaluated using the potential ecological risk factor (Eri) and modified ecological risk index (MRI). The single-element pollution indices indicated that the sediment has no significant pollution by individual elements. However, the multi-elemental approach shows slight pollution in the sediment core. The ecology is at low risk by contaminants present in the sediment. Comparison of the elemental values of shelf sediment with adjacent riverine and estuarine samples demonstrates the role of estuarine environment and/or high riverine flux of sediments causing either removal or dilution of trace elements during its transport from the river to the sea.

A Novel Synthesis of the Graphene Oxide-Silver (GO-Ag) Nanocomposite for Unique Physiochemical Applications.

Graphene oxide-silver nanocomposite (GO-Ag) was fabricated via the sonochemical method, which shows unique physiochemical properties. Graphene oxide (GO) and silver nanoparticles (AgNPs) were synthesized by modified Hummer's and Chemical reduction methods, respectively. The synthesized nanocomposite was characterized using powder X-ray diffraction, Raman spectroscopy, and Fourier-transform infrared spectroscopy. The surface morphology of synthesized nanoparticles was studied using scanning electron microscopy and transmission electron microscopy. The thermoluminescence property of the nanocomposite was analyzed by irradiating the samples in gamma radiation at 1 kGy. Electrochemical reversibility of the GO-Ag nanocomposite was examined by cyclic voltammetry. The photocatalytic application of the nanocomposite was studied using degradation of methylene blue dye. Results reveal that doping of AgNPs on the GO surface not only improves its dye degradation property but also enhances its thermoluminescence property. This knowledge will be helpful in determining the antibacterial property of the GO-Ag nanocomposite in the future.

Investigations of the heterometallic ludwigite Ni2AlBO5.

We present magnetic, thermodynamic, dielectric and structural investigations on the aluminoborate Ni2AlBO5, belonging to the ludwigite family. Room temperature structural refinement suggests that the system crystallizes in the orthorhombic Pbam symmetry, in similarity with most members of this material class. Magnetic and thermodynamic measurements shows that the system undergoes a phase transition to an antiferromagnetic state at 38 K, signatures of which are also seen in the lattice parameters and the dielectric constant. Short range magnetic correlations appear to persist to much higher temperatures-a regime in which the ac susceptibility exhibits a power law temperature dependence, in agreement with that expected for random exchange Heisenberg antiferromagnetic spin chains.

Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs.

BACKGROUND: Dishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases. METHODS: Shotgun proteomics including TiO2 enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on immunoprecipitates from HEK293T cells was used to identify and quantify phosphorylation of DVL3 protein induced by 8 kinases. Functional characterization was performed by in-cell analysis of phospho-mimicking/non-phosphorylatable DVL3 mutants and supported by FRET assays and NMR spectroscopy. RESULTS: We used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced ß-catenin activation. S630-643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization. CONCLUSIONS: We identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome. Video Abtract.

Delving into the Antiurolithiatic Potential of Tribulus terrestris Extract Through -In Vivo Efficacy and Preclinical Safety Investigations in Wistar Rats.

Modern treatment interventions for kidney stones are wrought with side-effects, hence the need for alternative therapies such as plant-based medicines. We have previously documented through in vitro studies that statistically optimized aqueous extract of Tribulus terrestris (Zygophyllaceae family) possesses antiurolithic and antioxidant potential. This provides strong scientific foundation to conduct in vivo efficacy and preclinical safety studies to corroborate and lend further proof to its ability to prevent and cure kidney stones. The preventive and curative urolithiatic efficacy in experimentally induced nephrolithiatic Wistar rats, along with preclinical toxicity was evaluated following oral administration of statistically optimized aqueous extract of T. terrestris. Treatment showed augmented renal function, restoration of normal renal architecture and increase in body weight. Microscopic analysis of urine revealed excretion of small sized urinary crystals, demonstrating that treatment potentially modulated the morphology of renal stones. Tissue enzymatic estimation affirmed the antioxidant efficacy of treatment with reduced free radical generation. Significant upregulation of p38MAPK at both the gene and protein level was noted in hyperoxaluric group and interestingly treatment reversed it. Acute oral toxicity study established the Median Lethal Dose (LD50) to be greater than 2000 mg/kg body weight (b.wt.) No observed adverse effect level (NOAEL) by repeated oral toxicity for 28 days at 750 mg/kg b.wt. was noted. This study lends scientific evidence to the safe, preventive and curative potential of statistically optimized aqueous extract of T. terrestris at a dose of 750 mg/kg b.wt. and suggests that the extract shows promise as a therapeutic antiurolithic agent.