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Several organisms, specifically microorganisms survive in a wide range of harsh environments including extreme temperature, pH, and salt concentration. We analyzed systematically a large number of protein sequences with their structures to understand their stability and to discriminate extremophilic proteins from their non-extremophilic orthologs. Our results highlighted that the strategy for the packing of the protein core was influenced by the environmental stresses through substitutive structural events through better ionic interaction. Statistical analysis showed that a significant difference in number and composition of amino acid exist among them. The negative correlation of pairwise sequence alignments and structural alignments indicated that most of the extremophile and non-extremophile proteins didn’t contain any association for maintaining their functional stability. A significant numbers of salt bridges were noticed on the surface of the extremostable proteins. The Ramachandran plot data represented more occurrences of amino acids being present in helix and sheet regions of extremostable proteins. We also found that a significant number of small nonpolar amino acids and moderate number of charged amino acids like Arginine and Aspartic acid represented more nonplanar Omega angles in their peptide bond. Thus, extreme conditions may predispose amino acid composition including geometric variability for molecular adaptation of extremostable proteins against atmospheric variations and associated changes under natural selection pressure. The variation of amino acid composition and structural diversifications in proteins play a major role in evolutionary adaptation to mitigate climate change.

We obtain the off‐shell nilpotent Becchi–Rouet–Stora–Tyutin (BRST) and anti‐BRST symmetry transformations (corresponding to the infinitesimal classical gauge symmetry transformations) for the modified massive three (2 + 1)‐dimensional (3D) Abelian two‐form gauge theory with a single pseudoscalar field. The latter field (having the negative kinetic term and a well‐defined rest mass) has already been shown (i) to exist in the modified version of the standard 3D Stückelberg formalism (on the solid mathematical grounds), (ii) to be a possible candidate for the “phantom” field of some of the cosmological models of the universe, and (iii) to be a possible candidate for dark matter. These three results have been indicated in our earlier work. A couple of novel observations in our present endeavor are (i) the observation that, even though the pseudoscalar field does not transform under the gauge and (anti‐)BRST symmetry transformations, it appears in the first‐class constraints which annihilate the physical states at the quantum level, and (ii) the Noether conserved (anti‐)BRST charges are found to be non-nilpotent . In our present investigation, the key results are the derivations of (i) the coupled (but equivalent) BRST and anti‐BRST invariant Lagrangian densities, (ii) the conserved and off‐shell nilpotent versions of the (anti‐)BRST charges and the conserved ghost charge, (iii) the (anti‐)BRST invariant Curci–Ferrari (CF) type restrictions, (iv) the standard BRST algebra amongst the conserved and nilpotent (anti‐)BRST charges and conserved ghost charge, and (v) the explicit BRST‐quantization of our 3D field‐theoretic system.

We report an easy to construct imaging system that can resolve particles separated by ≥ 0.68 μ m with minimum aberrations. Its first photon collecting lens is placed at a distance of 31.6 mm giving wide optical access. The microscope has a Numerical Aperture (NA) of 0.33, which is able to collect signal over 0.36 sr. The diffraction limited objective and magnifier recollects 77% photons into the central disc of the image with a transverse spherical aberration of 0.05 mm and magnification upto 238. The system has a depth of field of 142 μ m and a field of view of 56 μ m which images a large ensemble of atoms. The imaging system gives a diffraction limited performance over visible to near-infrared wavelengths on optimization of the working distance and the distance between the objective and magnifier.

Capacitive, inductive and resistive loads of an ion-trap system, which can be modelled as LCR circuits, are important to know for building a high accuracy experiment. Accurate estimation of these loads is necessary for delivering the desired radio frequency (RF) signal to an ion trap via an RF resonator. Of particular relevance to the trapped ion optical atomic clock, determination of these loads lead to accurate evaluation of the Black-Body Radiation (BBR) shift resulting from the inaccurate machining of the ion-trap itself. We have identified different sources of these loads and estimated their values using analytical and finite element analysis methods, which are found to be well in agreement with the experimentally measured values. For our trap geometry, we obtained values of the effective inductive, capacitive and resistive loads as: 3.1  μ H, 3.71 (1)  μ H, 3.68 (6)  μ H; 50.4 pF, 51.4 (7) pF, 40.7 (2) pF; and 1.373 Ω, 1.273 (3) Ω, 1.183 (9) Ω by using analytical, numerical and experimental methods, respectively. The BBR shift induced by the excess capacitive load arising due to machining inaccuracy in the RF carrying parts has been accurately estimated, which results to a fractional frequency shift of 6.6 × 10 −17 for an RF of 1 kV at 2 π  × 15 MHz and with ±10  μ m machining inaccuracy. This needs to be incorporated into the total systematic uncertainty budget of a frequency standard as it is about one order of magnitude higher than the present precision of the trapped ion optical clocks.

The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough. The present study is designed to substantiate the potential of D. burmannii in in vitro anticancer activity and its relation with anti-inflammatory property. In vitro anticancer study revealed that DBME is inhibiting the proliferation of MCF-7 cells without affecting the viability of other malignant and non-malignant cells. DBME induced G2/M phase arrest and apoptosis in MCF-7 cells by suppressing the expression of cyclin A1, cyclin B1 and Cdk-1 and increasing the expression of p53, Bax/Bcl-2 ratio leading to activation of caspases and PARP degradation. Presence of caspase-8 (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors alone did prevent the apoptosis partially while apoptosis prevention was significantly observed when used in combination, suggesting vital role of caspases in DBME-induced apoptosis in MCF-7 cells. DBME also downregulated LPS-induced increased expression of iNOS, COX-2 and TNF- α along with suppression on intracellular ROS production that confirms the potential of DBME as anti-inflammatory extract. GCMS analysis revealed the presence of four major compounds hexadecanoic acid, tetradecanoic acid, hexadecen-1-ol, trans-9 and 1-tetradecanol along with some other fatty acid derivatives and carotenoids (Beta-doradecin) in DBME. These findings confirmed the anti-inflammatory activity of DBME, which is already listed in French Pharmacopeia in 1965. Here we have additionally reported the anti-breast cancer activity of DBME and its relation to the anti-inflammatory potential. Hence, an ethnopharmacological approach can be considered as useful tool for the discovery of new drug leads.

In this work, we introduced a simple aggregation-induced emission enhancement (AIEE) sensor ( PHCS) which can selectively detect and discriminate three environmentally and biologically imperative heavy metal ions (Cu 2+ , Co 2+ and Hg 2+ ) and a hazard class 1 categorized nitro-explosive picric acid (PA) in differential media. By virtue of its weak fluorescence attributes in pure organic medium owing to the synergistic operation of multiple photophysical quenching mechanisms, the molecular probe showcased highly selective ‘TURN ON’ fluorogenic response towards hazardous Hg 2+ with a limit of detection (LOD) as low as 97 nM. Comprehensive investigation of binding mechanism throws light on the cumulative effect of probe-metal complexation induced chelation enhanced fluorescence (CHEF) effect and subsequent AIEE activation within the formed probe-metal adducts. Noteworthily, the probe ( PHCS ) can be readily used in real water samples for the quantitative determination of Hg 2+ in a wide concentration range. In addition, the probe displayed modest colorimetric recognition performances to selectively detect and discriminate two essential heavy metal ions (Cu 2+ and Co 2+ ) with a LOD of 96 nM and 65 nM for Cu 2+ and Co 2+ respectively, in semi-aqueous medium. Intriguingly, based on high photoluminescence efficiency, the AIEE active nano-aggregated PHCS displayed a remarkable propensity to be used as a selective and ultra-sensitive ‘TURN-OFF’ fluorogenic chemosensor towards PA with LOD of 34.4 ppb in aqueous medium. Finally, we specifically shed light on the interaction of PHCS hydrosol towards PA using some unprecedented techniques, which helped uncover new photophysical insights of probe-explosive molecule interaction. Graphical Abstract We shed light on novel photophysical insights toward unique multifunctional sensory aptitude of a simple aggregation-induced emission enhancement active organic functional molecule in differential media, enabling ultra-sensitive discriminative detection of toxic heavy metal ions and explosive molecule simultaneously.

Background: Serum tumor markers are beneficial to patients with advanced cancer because they help in early diagnosis, determining prognosis, predicting response to certain medications, and monitoring therapy. The prognostic value of cancer antigen 15-3 (CA15-3) serum-level changes in breast cancer is very well established. The main cause behind the elevation of CA 15-3 is metastatic breast carcinoma. In this study, we will run a record review to study comprehensively the clinical association between chronic myeloid disorders and CA15-3 elevation.Method: In this retrospective study, we run CA15-3 on 106 patients with different myeloid disorders diagnosed between 2008 and 2021 from several tertiary care centers in Saudi Arabia, Jeddah, majority of which (38 cases) were diagnosed with chronic myeloid leukemia (35.8%). Others had essential thrombocytosis (22.6%), chronic myeloproliferative neoplasm (20.8%), myelofibrosis (7.5%), acute myeloid leukemia (4.7%), myelodysplastic syndrome (4.7%), and polycythemia vera (3.8%).Result: An increase in CA15-3 was seen in 50% of all cases. In particular, polycythemia vera showed an elevation in 100% of the cases (4 out of 4). Second in expressivity is myelodysplastic syndrome (80%, 4 out of 5 cases). Close in value is myelofibrosis (75%, 6 out of 8 cases). The least association is noted between CA15-3 and essential thrombocytosis (16.7%, 4 out of 24 cases).Conclusion: When CA15-3 levels are considered during the time of myeloid disorder diagnosis, it shows an independent predictive value. More research is needed to determine the utility of these serum biomarkers in myeloid disorders decision-making. This is a thorough case series of chronic myeloid disorders inclusive of all myeloproliferative neoplasms besides myelodysplastic syndrome describing the association with CA15-3.

Abstract Disclosure: S. Haider: None. R.E. Thomas: None. E.D. Reed: None. S. Panja: None. 31-year-old F with PMH of obesity presented with intractable nausea and vomiting. Pt was initiated on semaglutide injections for weight loss by her PCP, however, given prohibitive costs and supply chain issues pt had not initiated her medication until a month later after purchasing from a compounding pharmacy. Her PCP sent instructions via text message after explaining in person at her initial evaluation.Pt was meant to initiate at 5 units (0.25mg/0.05ml) SQ, however mistakenly injected 50 units (2.5mg/0.5ml) after misreading the text message.Shortly thereafter pt began experiencing intense nausea followed by recurrent emesis. Vitals on admission significant for tachycardia. Labs showed gradually falling blood sugars (107, 91, 73). In the ED patient received IVF and a D5% NS drip was started to head off hypoglycemia. She was given Zofran and Reglan alongside meals in order to transition to, and sustain PO intake. On this regimen pt was able to tolerate a diet.Her blood sugars were monitored and improved as did her medical condition. Pt was discharged home and instructed to return should her symptoms recur. Pt opted to stop home semaglutide and follow up with PCP. She was prescribed PO Zofran and Reglan PRN with meals until PCP visit and telemetry verified QTc was not prolonged. This case report is to highlight the dangers of compounded semaglutide. Its ease of acquisition coupled with unregulated formulations, unknown effectiveness and unpredictable side effects are alarming. Ethical concerns arise as the overwhelming need for semaglutide’s compounded formulations may not be to lower morbidity and mortality, and shortages are occurring due to increased general population awareness of the weight loss benefits. Concerns include the possibility of incorrect formulations containing too little, too much or no active ingredient at all. These all lead to questions on effectiveness and long-term side effects. In addition to poor patient side effect and administration understanding, the potential for misuse and harm is increased multiple fold with unregulated compounding pharmacies advertising the medication.At present, all doses of Wegovy are in short supply with the exception of 2.4 mg/0.75 mL. This has spurred the FDA to authorize compounding pharmacies to produce and market additional doses. Wegovy is specifically approved for weight loss unlike Ozempic, another GLP-1 agonist, which is only approved for type 2 Diabetes. According to the FDA: Regarding compounded Semaglutide, the FDA has received reports that in some cases, compounders may be using salt forms of semaglutide, including semaglutide sodium and acetate. The salt forms are different active ingredients than those used the approved drug, (which contain the base form of semaglutide). The FDA is not aware of any basis for compounding using the salt forms that would meet the FD&C requirements for types of active ingredients that can be compounded. Presentation: 6/3/2024

An expanding corpus of evidence suggests that zinc finger DHHC-type palmitoyltransferase 9 (ZDHHC9) may represent a promising biomarker in various malignancies. Noteworthy is the fact that ZDHHC9 has been discovered to be significantly upregulated in specific varieties of human gastrointestinal cancers. Nevertheless, the precise role it plays in tumor prognostic evaluation and diagnostic identification remains ambiguous. In this study, we commenced with a thorough investigation of ZDHHC9 expression by leveraging the extensive and comprehensive TCGA database. This resource offers a wealth of valuable information and data samples, which enabled a more comprehensive and thorough analysis. The expression levels of ZDHHC9 in BRCA, CESC, HNSC, and KIRP were thoroughly investigated, revealing a significant elevation compared to normal tissues. This significant escalation was observed to be intimately linked with an adverse prognosis. A comprehensive analysis of the data revealed that the increased expression of ZDHHC9 in these particular cancer types was associated with poorer outcomes for patients. The extensive study examining various cancer types has yielded significant insights regarding the function of ZDHHC9, as well as its potential implications for prognosis and therapeutic strategies. Functional predictions indicate that immune or metabolic disorders, as well as the activation of carcinogenic signaling pathways due to abnormal expression of ZDHHC9, may significantly contribute to tumor progression and poor prognosis in patients. This further corroborates the influence of ZDHHC9 on the migration and invasion capabilities of CESC cell lines. ZDHHC9 is a key target for therapeutic and diagnostic use in BRCA, CESC, HNSC, and KIRP tumors, contributing significantly to the understanding of molecular tumor treatments.