PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis. Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed. Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy. Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

Role of artificial intelligence, machine learning and deep learning models in corneal disorders - A narrative review.

In the last decade, artificial intelligence (AI) has significantly impacted ophthalmology, particularly in managing corneal diseases, a major reversible cause of blindness. This review explores AI's transformative role in the corneal subspecialty, which has adopted advanced technology for superior clinical judgment, early diagnosis, and personalized therapy. While AI's role in anterior segment diseases is less documented compared to glaucoma and retinal pathologies, this review highlights its integration into corneal diagnostics through imaging techniques like slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal biomicroscopy. AI has been pivotal in refining decision-making and prognosis for conditions such as keratoconus, infectious keratitis, and dystrophies. Multi-disease deep learning neural networks (MDDNs) have shown diagnostic ability in classifying corneal diseases using AS-OCT images, achieving notable metrics like an AUC of 0.910. AI's progress over two decades has significantly improved the accuracy of diagnosing conditions like keratoconus and microbial keratitis. For instance, AI has achieved a 90.7% accuracy rate in classifying bacterial and fungal keratitis and an AUC of 0.910 in differentiating various corneal diseases. Convolutional neural networks (CNNs) have enhanced the analysis of color-coded corneal maps, yielding up to 99.3% diagnostic accuracy for keratoconus. Deep learning algorithms have also shown robust performance in detecting fungal hyphae on in vivo confocal microscopy, with precise quantification of hyphal density. AI models combining tomography scans and visual acuity have demonstrated up to 97% accuracy in keratoconus staging according to the Amsler-Krumeich classification. However, the review acknowledges the limitations of current AI models, including their reliance on binary classification, which may not capture the complexity of real-world clinical presentations with multiple coexisting disorders. Challenges also include dependency on data quality, diverse imaging protocols, and integrating multimodal images for a generalized AI diagnosis. The need for interpretability in AI models is emphasized to foster trust and applicability in clinical settings. Looking ahead, AI has the potential to unravel the intricate mechanisms behind corneal pathologies, reduce healthcare's carbon footprint, and revolutionize diagnostic and management paradigms. Ethical and regulatory considerations will accompany AI's clinical adoption, marking an era where AI not only assists but augments ophthalmic care.

Biofilms from poly-vinyl alcohol/palmyra root sprout with Boswellia serrata, carbon dots and anthocyanin for sensing the freshness of sardine fish.

One of the main issues that customers worldwide have is food adulteration. In commercial packages, freshness cannot always be determined visually. Here, we propose sensitive films for use in food packaging that could alter colour to indicate a change in freshness. Hybrid, multifunctional, and eco-friendly films were prepared from polyvinyl alcohol/palmyra root sprout (PVA/PRS), fused with soy protein isolate carbon dot (CD), Boswellia serrata (BS), and Clitoriaternatea anthocyanin (CTE). The films showed pH sensitivity, antioxidant, and UV barrier properties. By creating hydrogen bonds between PRS and the other fillers, adding these substances makes PVA less crystallized. These interactions were verified by infrared Fourier-transform analysis. When compared to PVA, PRS films had significantly lower moisture content and swelling ratios. The UV-blocking capabilities of the films were greatly improved by the addition of CD, BS, and CTE without compromising their mechanical, thermal, or water vapor barrier properties. The composite film PVA/PRS/CD/BS/CTE exhibited a maximum tensile strength value of 69.47 ± 1.49 MPa. The CT extract provides the film with superior antioxidant properties. The colorimetric films PVA/PRS/CTE and PVA/PRS/CD/BS/CTE showed distinct pH-responsive colour-change properties as well as good colour stability. The colorimetric films were used to test the freshness of sardine fish, and they revealed unique colour changes that indicated whether the fish sample was spoiled or not.

Involvement of ObRb receptor, nitric oxide, and BKCa channel signaling pathways in leptin-induced relaxation of pregnant mouse uterus.

The purpose of this study was to determine the receptor subtype and the underlying mechanisms involved in the relaxant effect to leptin in mid- and late-pregnant mouse uterus. We determined the relative mRNA expression of receptor subtypes, eNOS, and BKCa channel by quantitative PCR and also the overall receptor expression by immunohistochemistry. Isometric tension studies were conducted to evaluate the effects of leptin and to delineate its mechanisms. A selective siRNA for the ObRb receptor was used to determine the participation of the receptor subtype in biochemical and molecular effects of leptin. The relaxant response to leptin was greater in mid-pregnancy compared to late pregnancy and was mediated by the activation of BKCa channels by eNOS-derived nitric oxide in an ObRb receptor-dependent manner. In comparison to mid-pregnancy, expression of short forms (mainly ObRa receptor) of the receptor was significantly increased in late pregnancy, whereas ObRb receptor expression was similar in both phases. The results of the study suggest that ObRb receptor mediates leptin-induced increase in eNOS expression and NO synthesis. Leptin-induced eNOS expression and activation cause cGMP-independent stimulation of BKCa channels causing uterine relaxation. Increased short forms of the receptors and reduced BKCa channels exert a negative effect on uterine relaxation in late pregnancy. Leptin may have a physiological role in maintaining uterine quiescence in mid-pregnancy and its reduced relaxant response in late gestation may facilitate labor. Further, ObRb receptor agonists may be useful in the management of preterm labor.

Structurally influenced optical nonlinearities and ultrafast dynamics in ß-acroleyl- and ß-dicyanobutadienyl-appended cobalt corroles.

The strong two-photon induced nonlinear absorption and self-focusing type positive nonlinear refraction are pronounced by the structural engineering in ß-functionalized cobalt corroles.

Spectrally resolved nonlinearities within a laser pulse in a single-scan and spectrometer-based nonlinear optical probing.

The intricate spectrally resolved optical nonlinearities resulting from a spectrally broad femtosecond Gaussian laser pulse have been unraveled using a single-scan and spectrometer-based nonlinear optical probing technique. The interaction of the broad femtosecond laser pulse with a strongly absorbing organic dye has unveiled a remarkably distinct nonlinear absorption behavior across the broad spectral window. The nonlinear absorption behavior unveils an unusual transition from the reverse saturation absorption (RSA) to the saturation absorption (SA) as we sweep the wavelength on both sides of the central wavelength of the excitation laser pulse. A competition between the band-filling and excited-state absorption results in such a dramatic switch-over from the RSA to the SA due to the variation of the intensity distribution across the Gaussian pulse spectrum. On the other hand, the nonlinear refraction studies dictate more over the constant Kerr-type positive nonlinear refractive indices across the entire laser pulse, with a pronounced contribution from the nonlinear absorption phase dominating at the center of the pulse. The presented technique establishes a robust and simple spectrometer-based technique that offers new, to the best of our knowledge, avenues for estimating optical nonlinearities for rapid nonlinear optical measurements.

Addition of Imidazolium-Based Ionic Liquid to Improve Methanol Production in Polyamine-Assisted CO2 Capture and Conversion Systems Using Pincer Catalysts.

Ionic liquids have been studied as CO2 capture agents. However, they are rarely used in combined CO2 capture and conversion processes. Utilizing imidazolium-based ionic liquids, the conversion of CO2 to methanol was greatly improved in polyamine assisted systems catalyzed by homogeneous pincer catalysts with Ru and Mn metal centers. Among the ionic liquids tested, [BMIM]OAc was found to perform the best under the given reaction conditions. Among the polyamine tested, pentaethylenehexamine (PEHA) led to the highest conversion rates. Ru-Macho and Ru-Macho-BH were the most active catalysts. Direct air capture utilizing PEHA as the capture material was also demonstrated and produced an 86 % conversion of the captured CO2 to methanol in the presence of [BMIM]OAc.

Syntheses, structural, photophysical and theoretical studies of heteroleptic cycloplatinated guanidinate(1-) complexes bearing acetylacetonate and picolinate ancillary ligands.

Cycloplatination of symmetrical N,N',N''-triarylguanidines, (ArNH)2C[double bond, length as m-dash]NAr with cis-[Pt(TFA)2(S(O)Me2)2] in toluene afforded cis-[Pt(TAG)(TFA)(S(O)Me2)] (TAG = triarylguanidinate(1-)-κC,κN; TFA = OC(O)CF3; 6-9) in 75-82% yields. The reactions of 6-9 and the previously known cis-[Pt(TAG)X(S(O)Me2)] (X = Cl (1) and TFA (2-5)) with acetylacetone (acacH) or 2-picolinic acid (picH) in the presence of a base afforded [Pt(TAG)(acac)] (acac = acetylacetonate-κ2O,O'; 10-18) and [Pt(TAG)(pic)] (pic = 2-picolinate-κN,κO; 19) in high yields. The new complexes were characterised by analytical, IR and multinuclear NMR spectroscopies. Further, molecular structures of 11, 12, 13·0.5 toluene and 14-19 were determined by single crystal X-ray diffraction. Absorption spectra of 10-19 in solution and their emission spectra in crystalline form were measured. Platinacycles 10-19 are bluish green light emitter in the crystalline form, and emit in the λPL = 488-529 nm range (11 and 13-19) while 12 emits at λPL = 570 nm. Unlike other platinacycles, the emission band of 12 is broad, red shifted, and this pattern is ascribed to the presence of an intermolecular N-H⋯Pt interaction involving the endocyclic amino unit of the six-membered [Pt(TAG)] ring and the Pt(ii) atom in the adjacent molecule in an asymmetric unit of the crystal lattice. Lifetime measurements were carried out for all platinacycles in crystalline form, which revealed lifetime in the order of nanoseconds. The origin of absorption and emission properties of 11, 15, 18 and 19 were studied by TD-DFT calculations.

Integrated Carbon Dioxide Capture and Conversion to Methanol Utilizing Tertiary Amines over a Heterogenous Cu/ZnO/Al2O3 Catalyst.

Increasing carbon dioxide emissions has sparked a growing interest in capturing these emissions at the source of their release. For such processes, amines can be used as carbon dioxide capture agents. Herein, CO2 was captured under ambient conditions using solutions of amines and polyamines in ethylene glycol. The captured solutions were then successfully hydrogenated to methanol under hydrogen pressure with a heterogeneous Cu/ZnO/Al2O3 industrial catalyst. An extensive amine scope found that tetramethyl-1,6-hexanediamine, with two tertiary amine sites, provided the highest methanol productivity. This reaction was then optimized to achieve up to 89% methanol yield under relatively mild conditions of 250 °C and 80 bar H2 pressure. The catalyst was shown to be recyclable over five reaction cycles.

Interplay of mitochondria-associated membrane proteins and autophagy: Implications in neurodegeneration.

Since the discovery of membrane contact sites between ER and mitochondria called mitochondria-associated membranes (MAMs), several pieces of evidence identified their role in the regulation of different cellular processes such as Ca2+ signalling, mitochondrial transport, and dynamics, ER stress, inflammation, glucose homeostasis, and autophagy. The integrity of these membranes was found to be essential for the maintenance of these cellular functions. Accumulating pieces of evidence suggest that MAMs serve as a platform for autophagosome formation. However, the alteration within MAMs structure is associated with the progression of neurodegenerative diseases. Dysregulated autophagy is a hallmark of neurodegeneration. Here, in this review, we highlight the present knowledge on MAMs, their structural composition, and their roles in different cellular functions. We also discuss the association of MAMs proteins with impaired autophagy and their involvement in the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Ultrafast Dynamics, Optical Nonlinearities, and Chemical Sensing Application of Free-Standing Porous Silicon-Based Optical Microcavities.

The present work demonstrates the ultrafast carrier dynamics and third-order nonlinear optical properties of electrochemically fabricated free-standing porous silicon (FS-PSi)-based optical microcavities via femtosecond transient absorption spectroscopy (TAS) and single-beam Z-scan techniques, respectively. The TAS (pump: 400 nm, probe: 430-780 nm, ∼70 fs, 1 kHz) decay dynamics are dominated by the photoinduced absorption (PIA, lifetime range: 4.7-156 ps) as well as photoinduced bleaching (PIB, 4.3-324 ps) for the cavity mode (λc) and the band edges. A fascinating switching behavior from the PIB (-ve) to the PIA (+ve) has been observed in the cavity mode, which shows the potential in ultrafast switching applications. The third-order optical nonlinearities revealed an enhanced two-photon absorption coefficient (ß) in the order of 10-10 mW-1 along with the nonlinear refractive index (n2) in the range of 10-17 m2 W-1. Furthermore, a real-time sensing application of such FS-PSi microcavities has been demonstrated for detecting organic solvents by simultaneously monitoring the kinetics in reflection and transmission mode.

Development of a pulse modulated sub-radio frequency power supply for atmospheric pressure plasma devices.

The effect of pulse-modulated sub-RF range (100 kHz-1 MHz) excitation on atmospheric pressure argon plasma jet characteristics is studied. For this, a suitable power supply is developed, offering a sub-µs rise time with control of different parameters, such as voltage amplitude, pulse modulation frequency in the range of 1-30 kHz, and an oscillation frequency of ∼520 kHz, which can affect the plasma behavior. Plasma characteristics, such as reactive species generation, ionic composition, plasma plume length, and gas temperature, are evaluated qualitatively and quantitatively by employing diagnostics such as optical emission spectroscopy, molecular beam mass spectrometry, and optical imaging. Experimental observations indicate that the gas temperature of the plasma jet and plume length increase with the applied voltage for all pulse modulation frequencies, with a maximum value of ∼(325 ± 2 K) and a maximum length of ∼(23 ± 3 mm), respectively, at 30 kHz and 9 kVpp. The emission intensities of OH• and O• lines show an incremental behavior with the applied voltage across all pulse modulation frequencies. The relative yield of different positive (OH+, O+, etc.) and negative (OH-, O-, etc.) ions also increases with the applied voltage for all pulse modulation frequencies with maximum values of ∼(7.6%, 9.9%) and (3.9%, 9.4%), respectively; these are relatively close to RF excited ionic concentrations reported previously. Attaining a high plasma length and species yield signify the features of both kHz and RF atmospheric plasmas. This study offers significant insights and flexibility into exploring the impact of different RF frequency regimes on plasma characteristics.

Anti-tubercular therapy (ATT) induced thrombocytopenia: A systematic review.

INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.

Genetic Enhancement for Biotic Stress Resistance in Basmati Rice through Marker-Assisted Backcross Breeding.

Pusa Basmati 1509 (PB1509) is one of the major foreign-exchange-earning varieties of Basmati rice; it is semi-dwarf and early maturing with exceptional cooking quality and strong aroma. However, it is highly susceptible to various biotic stresses including bacterial blight and blast. Therefore, bacterial blight resistance genes, namely, xa13 + Xa21 and Xa38, and fungal blast resistance genes Pi9 + Pib and Pita were incorporated into the genetic background of recurrent parent (RP) PB1509 using donor parents, namely, Pusa Basmati 1718 (PB1718), Pusa 1927 (P1927), Pusa 1929 (P1929) and Tetep, respectively. Foreground selection was carried out with respective gene-linked markers, stringent phenotypic selection for recurrent parent phenotype, early generation background selection with Simple sequence repeat (SSR) markers, and background analysis at advanced generations with Rice Pan Genome Array comprising 80K SNPs. This has led to the development of Near isogenic lines (NILs), namely, Pusa 3037, Pusa 3054, Pusa 3060 and Pusa 3066 carrying genes xa13 + Xa21, Xa38, Pi9 + Pib and Pita with genomic similarity of 98.25%, 98.92%, 97.38% and 97.69%, respectively, as compared to the RP. Based on GGE-biplot analysis, Pusa 3037-1-44-3-164-20-249-2 carrying xa13 + Xa21, Pusa 3054-2-47-7-166-24-261-3 carrying Xa38, Pusa 3060-3-55-17-157-4-124-1 carrying Pi9 + Pib, and Pusa 3066-4-56-20-159-8-174-1 carrying Pita were identified to be relatively stable and better-performing individuals in the tested environments. Intercrossing between the best BC3F1s has led to the generation of Pusa 3122 (xa13 + Xa21 + Xa38), Pusa 3124 (Xa38 + Pi9 + Pib) and Pusa 3123 (Pi9 + Pib + Pita) with agronomy, grain and cooking quality parameters at par with PB1509. Cultivation of such improved varieties will help farmers reduce the cost of cultivation with decreased pesticide use and improve productivity with ensured safety to consumers.

Silver-Gold Alloy Nanoparticles (AgAu NPs): Photochemical Synthesis of Novel Biocompatible, Bimetallic Alloy Nanoparticles and Study of Their In Vitro Peroxidase Nanozyme Activity.

Facile synthesis of metal nanoparticles with controlled physicochemical properties using environment-friendly reagents can open new avenues in biomedical applications. Nanomaterials with controlled physicochemical properties have opened new prospects for a variety of applications. In the present study, we report a single-step photochemical synthesis of ~5 nm-sized silver (Ag) and gold (Au) nanoparticles (NPs), and Ag-Au alloy nanoparticles using L-tyrosine. The physicochemical and surface properties of both monometallic and bimetallic NPs were investigated by analytical, spectroscopic, and microscopic techniques. Our results also displayed an interaction between L-tyrosine and surface atoms that leads to the formation of AgAu NPs by preventing the growth and aggregation of the NPs. This method efficiently produced monodispersed NPs, with a narrow-sized distribution and good stability in an aqueous solution. The cytotoxicity assessment performed on breast cancer cell lines (MCF-7) revealed that the biofriendly L-tyrosine-capped AgNPs, AuNPs, and bimetallic AgAu NPs were biocompatible. Interestingly, AgAu NPs have also unveiled controlled cytotoxicity, cell viability, and in vitro peroxidase nanozyme activity reliant on metal composition and surface coating.

Germylenes Exhibiting Solid-State Emissions that Extend to NIR.

Low-valent main group compounds that fluoresce in the solid-state were previously unknown. To address this, we investigated room-temperature photoluminescence from a series of crystals of germylenes 3-8 in this article; they exhibited emissions nearly reaching the NIR. Germylene carboxylates (3-8) were synthesized by reacting dipyrromethene stabilized germylene pyrrolide (2) with carboxylic acids such as acetic acid, trifluoroacetic acid, benzoic acid, p-cyanobenzoic acid, p-nitrobenzoic acid, and acetylsalicylic acid.

Enhanced Femtosecond Nonlinearities and Multiphoton Absorptions in Discrete Bands of Porphyrins.

Optical nonlinearities of discrete absorption energy levels of one of the typical heterocyclic aromatic molecules, free-base porphyrins, have been probed over a broad spectral region (400-1600 nm) utilizing intense femtosecond pulses. A wide range of strong one- and multiphoton-induced nonlinear absorptions of both the blue-end Soret (B) band (au → b1g) and red-end orbital mixing split quasi-allowed Q-bands (Qx(0,0; 0,1), Qy(0,0; 0,1), au → eg) are critically probed and reported. During the resonant excitation within B- (400 nm) and Q-bands (600-750 nm), the nonlinear absorption has become predominant by the saturation of absorption (SA) of the one-photon absorption (1PA) process due to ground-state bleaching. At nonresonant wavelengths, it is dominated by the reverse saturation of absorption (RSA), involving various nonlinear processes of two-, three-, and four-photon (2PA, 3PA, and 4PA) absorptions, either to B- or Q-bands (1100-1600 nm). The laser intensity-dependent nonresonant (2PA, 800 nm) excitations for the prominent B-band show a distinct cross-over from SA to RSA, contributed by the excited-state absorption (ESA) utilizing a three-photon induced (3PA) process, whereas resonant (1PA, 400 nm) excitation reveals a systematic strong SA process. Both wavelength- and intensity-dependent nonlinear refractive index studies exhibit positive electronic Kerr-based self-focusing effects, with prominent contributions of nonlinear absorption and higher-order effects. The spectrally discrete, highly intense laser probing of individual energy bands and the consequent variety of nonlinearities can be broadly generalized for many free-base porphyrins and metalloporphyrins. The present studies provide a strong foundation and new insight into the broad categories of macrocycles, such as porphyrins and phthalocyanines, for myriad applications in nonlinear optics and bio/optophotonics.

Profiling of Antimicrobial Resistance Genes and Integron from Escherichia coli Isolates Using Whole Genome Sequencing.

This study is designed to investigate Escherichia coli for the antibiotic resistance genes (ARGs) and integrons from healthy as well as diarrhoeic/diseased animals/birds' faecal samples. A total of eight samples were selected for the study; from each animal, two samples were taken, one from healthy animals/birds and one from diarrhoeic/diseased animals/birds. Antibiotic sensitivity testing (AST) and whole genome sequencing (WGS) was performed for selected isolates. The E. coli isolates showed resistance to moxifloxacin, followed by erythromycin, ciprofloxacin, pefloxacin, tetracycline, levofloxacin, ampicillin, amoxicillin, and sulfadiazine (4/8, 50.00% each). The E. coli isolates were 100% sensitive to amikacin, followed by chloramphenicol, cefixime, cefoperazone, and cephalothin. A total of 47 ARGs from 12 different antibiotic classes were detected among the eight isolates by WGS. The different classes of antibiotics included aminoglycoside, sulphonamide, tetracycline, trimethoprim, quinolone, fosfomycin, phenicol, macrolide, colistin, fosmidomycin, and multidrug efflux. The class 1 integrons were detected in 6/8 (75.00%) isolates with 14 different gene cassettes.