Triple Nucleophilic Head-to-Tail Cascade Polycyclization of Diazodienals via Combination Catalysis: Direct Access to Cyclopentane Fused Aza-Polycycles with Six-Contiguous Stereocenters.

Reported herein are the bench stable (2E,4E)-diazohexa-2,4-dienals (diazodienals) and their unprecedented polycyclization with aldimine and arylamines enabled by Rh(II)/Brønsted acid relay catalysis. This scalable and atom-economical reaction provides direct access to the biologically important azatricyclo[6.2.1.04,11]undecane fused polycycles having six-contiguous stereocenters. Mechanistic studies revealed that polycyclization proceeds through an unusual triple-nucleophilic cascade initiated by aldimine attack on remote Rh-carbenoid, 6π-electrocyclization of aza-trienyl azomethine ylide, stereoselective aza-Michael addition via iminium activation, and inverse electron-demand intramolecular aza Diels-Alder reaction. The π-π secondary interactions play a crucial role in the preorganization of reactive intermediates for the pericyclic reactions and, hence, the overall efficiency of the polycyclization.

Comparative analysis of Doxycycline and Ayurvedic herbs to target metastatic breast cancer: An in-silico approach.

Background: Metastasis of breast cancer cells to distant sites including lungs, liver, lymph node, brain and many more have substantially affected the overall survival outcome and distant metastasis free survival rate amongst the diseased individuals. Several pre-clinical and clinical studies were carried out to determine the potency of vigorous inhibitors but they extensively deteriorated the patient's quality of life. Hence, there exists an urgent need to explore potent natural remedy to fight against metastatic breast cancer. Methods: Ayurvedic medicinal plants documented in literature for their ability to fight against breast cancer was screened and their respective active moieties were evaluated to exert inhibitory effect against MMP9. Drug like efficacy of phytochemicals were determined using Molecular docking, MD Simulation, ADMET and MM-PBSA and were further compared with synthetic analogs i.e. Doxycycline. Results: Out of 1000 phytochemicals, 12 exerted highest binding affinity (BA) even more than -9.0 kcal/mol that was significantly higher in comparison to Doxycycline which exhibited BA of -7.3 kcal/mol. In comparison to 37 × 30 × 37 Å, 53 × 45 × 66 Å offered best binding site and the highest BA was exhibited by Viscosalactone at LYS104, ASP185, MET338, LEU39, ASN38. During MD Simulation, Viscosalactone-MMP9 complex remained stable for 20 ns and the kinetic, electrostatic and potential energies were observed to be better than Doxycycline. Furthermore, Viscosalactone obtained from Withania somnifera justified the Lipinski's Rule of 5. Conclusion: Viscosalactone obtained from W. somnifera may act as promising drug candidate to fight against metastatic breast cancer.

Electrochemically-driven difunctionalization of the isocyanide and Mumm rearrangement cascade: expeditious synthesis of N-acyl-N-alkyl S-thiocarbamates.

We describe the novel electrochemical multicomponent reaction (e-MCR) of readily available isocyanides, thiols and carboxylic acids to form N-substituted S-thiocarbamate derivatives that are found in several biologically active compounds. The effectiveness of the µ-electro flow reactor (µ-EFR) was showcased through significant reduction in electrolyte volume during the reaction, achieving gram-scale production of 4a within a short 12 min residence time using a Pt/Pt flow cell.

Longitudinal assessment of extreme climate events in Kinnaur district, Himachal Pradesh, north-western Himalaya, India.

It is vital to keep an eye on changes in climatic extremes because they set the stage for current and potential future climate, which usually have a reasonable adverse impact on ecosystems and society. The present study examines the variability and trends in precipitation and temperature across seasons in the Kinnaur district, offering valuable insights into the complex dynamics of the Himalayan climate. Using Climatic Research Unit gridded Time Series (CRU TS) datasets from 1951 to 2021, the study analyzes the data to produce 28 climate indices based on India Meteorological Department (IMD) convention indices and Expert Team on Climate Change Detection and Indices (ETCCDI). Although there may be considerable variation in climate indices in terms of absolute values within different products, there is consensus in both long-term trends and inter-annual variability. Analysis shows that even within a small area, there is variability in the magnitude and direction of historic temperature trends. Initially, the data were subjected to rigorous quality control procedures, which involved identifying anomalies. Statistical analysis like trend analysis, employing Mann-Kendall test and Sen's slope estimator, reveal significant (p < 0.05) increase in consecutive dry days (CDD) at 0.03 days/year and decrease in consecutive wet days (CWD) at 0.02 days/year. Notably, the frequency of heavy precipitation occurrences showed an increasing trend. Changes in precipitation in the Western Himalaya are driven by a complex interplay of orographic effects, monsoonal dynamics, atmospheric circulation patterns, climate change, and localized factors such as topography, atmospheric circulation patterns, moisture sources, land-sea temperature contrasts, and anthropogenic influences. Moreover, in case of temperature indices, there is significant increasing trend observed. Temperature indices indicate a significant annual increase in warm nights (TN90p) at 0.06%/year and warm days (TX90p) at 0.11%/year. Extreme temperature events have been trending upward, with monthly daily maximum temperature (TXx) increasing by 1.5 °C yearly. This study enhances our comprehension of the global warming phenomenon and underscores the importance of acknowledging alterations in the water cycle and their repercussions on hydrologic resources, agriculture, and livelihoods in the cold desert of the northwestern Indian Himalaya.

Fostering Charge Carrier Transport and Absorber Growth Properties in CZTSSe Thin Films with an ALD-SnO2 Capping Layer.

The present study demonstrates that precursor passivation is an effective approach for improving the crystallization process and controlling the detrimental defect density in high-efficiency Cu2ZnSn(S,Se)4 (CZTSSe) thin films. It is achieved by applying the atomic layer deposition (ALD) of the tin oxide (ALD-SnO2) capping layer onto the precursor (Cu-Zn-Sn) thin films. The ALD-SnO2 capping layer was observed to facilitate the homogeneous growth of crystalline grains and mitigate defects prior to sulfo-selenization in CZTSSe thin films. Particularly, the CuZn and SnZn defects and deep defects associated with Sn were effectively mitigated due to the reduction of Sn2+ and the increase in Sn4+ levels in the kesterite CZTSSe film after introducing ALD-SnO2 on the precursor films. Subsequently, devices integrating the ALD-SnO2 layer exhibited significantly reduced recombination and efficient charge transport at the heterojunction interface and within the bulk CZTSSe absorber bulk properties. Finally, the CZTSSe device showed improved power conversion efficiency (PCE) from 8.46% to 10.1%. The incorporation of ALD-SnO2 revealed reduced defect sites, grain boundaries, and surface roughness, improving the performance. This study offers a systematic examination of the correlation between the incorporation of the ALD-SnO2 layer and the improved PCE of CZTSSe thin film solar cells (TFSCs), in addition to innovative approaches for improving absorber quality and defect control to advance the performance of kesterite CZTSSe devices.

Is Deep margin elevation a reliable tool for cervical margin relocation? - A comparative review.

The permanence of deep subgingival restorations are questionable both functionally and biologically. Crown lengthening is one of the traditionally performing procedures to visualize and relocate the deep margins, but the limitations of the invasive surgical procedure are anatomical complications like exposure of root concavities or furcation, violation of biological width, post operative discomfort because of sutures or periodontal packs; and less patient compliance. Other than crown lengthening, researchers tried some other techniques like modified matrix adaptation technique, using retraction cord, making holes in matrix band and flowing resin modified glass ionomer cement (RMGIC) to the root or cervical caries, orthodontic extrusion. But most of these procedures are failed to give adequate clinical success. Deep margin elevation (DME) is one of the minimally invasive and successful procedure performing in deep subgingival caries. But the evidences and knowledge in this technique is limited among practitioners. This review is to evaluate the applicability of DME, the current clinical concepts, techniques and materials for DME; and a comparison with traditionally used various techniques for cervical margin relocation also concluding that currently available various clinical parameters with this technique.

Lung type 3 innate lymphoid cells respond early following Mycobacterium tuberculosis infection.

Tuberculosis is the leading cause of death due to an infectious disease worldwide. Innate lymphoid type 3 cells (ILC3s) mediate early protection during Mycobacterium tuberculosis (Mtb) infection. However, the early signaling mechanisms that govern ILC3 activation or recruitment within the lung during Mtb infection are unclear. scRNA-seq analysis of Mtb-infected mouse lung innate lymphoid cells (ILCs) has revealed the presence of different clusters of ILC populations, suggesting heterogeneity. Using mouse models, we show that during Mtb infection, interleukin-1 receptor (IL-1R) signaling on epithelial cells drives ILC3 expansion and regulates ILC3 accumulation in the lung. Furthermore, our data revealed that C-X-C motif chemokine receptor 5 (CXCR5) signaling plays a crucial role in ILC3 recruitment from periphery during Mtb infection. Our study thus establishes the early responses that drive ILC3 accumulation during Mtb infection and points to ILC3s as a potential vaccine target. IMPORTANCE: Tuberculosis is a leading cause of death due to a single infectious agent accounting for 1.6 million deaths each year. In our study, we determined the role of type 3 innate lymphoid cells in early immune events necessary for achieving protection during Mtb infection. Our study reveals distinct clusters of ILC2, ILC3, and ILC3/ILC1-like cells in Mtb infection. Moreover, our study reveal that IL-1R signaling on lung type 2 epithelial cells plays a key role in lung ILC3 accumulation during Mtb infection. CXCR5 on ILC3s is involved in ILC3 homing from periphery during Mtb infection. Thus, our study provides novel insights into the early immune mechanisms governed by innate lymphoid cells that can be targeted for potential vaccine-induced protection.

A precise model for skin cancer diagnosis using hybrid U-Net and improved MobileNet-V3 with hyperparameters optimization.

Skin cancer is a frequently occurring and possibly deadly disease that necessitates prompt and precise diagnosis in order to ensure efficacious treatment. This paper introduces an innovative approach for accurately identifying skin cancer by utilizing Convolution Neural Network architecture and optimizing hyperparameters. The proposed approach aims to increase the precision and efficacy of skin cancer recognition and consequently enhance patients' experiences. This investigation aims to tackle various significant challenges in skin cancer recognition, encompassing feature extraction, model architecture design, and optimizing hyperparameters. The proposed model utilizes advanced deep-learning methodologies to extract complex features and patterns from skin cancer images. We enhance the learning procedure of deep learning by integrating Standard U-Net and Improved MobileNet-V3 with optimization techniques, allowing the model to differentiate malignant and benign skin cancers. Also substituted the crossed-entropy loss function of the Mobilenet-v3 mathematical framework with a bias loss function to enhance the accuracy. The model's squeeze and excitation component was replaced with the practical channel attention component to achieve parameter reduction. Integrating cross-layer connections among Mobile modules has been proposed to leverage synthetic features effectively. The dilated convolutions were incorporated into the model to enhance the receptive field. The optimization of hyperparameters is of utmost importance in improving the efficiency of deep learning models. To fine-tune the model's hyperparameter, we employ sophisticated optimization methods such as the Bayesian optimization method using pre-trained CNN architecture MobileNet-V3. The proposed model is compared with existing models, i.e., MobileNet, VGG-16, MobileNet-V2, Resnet-152v2 and VGG-19 on the "HAM-10000 Melanoma Skin Cancer dataset". The empirical findings illustrate that the proposed optimized hybrid MobileNet-V3 model outperforms existing skin cancer detection and segmentation techniques based on high precision of 97.84%, sensitivity of 96.35%, accuracy of 98.86% and specificity of 97.32%. The enhanced performance of this research resulted in timelier and more precise diagnoses, potentially contributing to life-saving outcomes and mitigating healthcare expenditures.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Development and Evaluation of Dutasteride Nanoemulgel for the Topical Delivery against Androgenic Alopecia.

BACKGROUND: Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have shown special interest in developing topical formulations for treating androgenic alopecia. Dutasteride emulsification may lead to good skin penetration and improved availability in different lipophilic skin environments. OBJECTIVES: This study aimed to encapsulate the drug into the lipidic carrier system for better local availability in the scalp skin, develop and evaluate nanoemulgel of dutasteride to ensure efficient topical administration, and perform the in-vivo activity of the developed gel for improved efficacy against alopecia. METHODS: Dutasteride-loaded nanoemulsion was prepared by a high-speed homogenizer, followed by thickening of the dispersion using Carbopol 934. Skin permeation and accumulation were investigated in the excised skin of male Swiss albino mice. The nanoemulgel was characterized based on pH, stress stability, viscosity, and hardness. RESULTS: The optimized dutasteride-loaded nanoemulsion had a size of 252.33 ± 8.59 nm, PDI of 0.205 ± 0.60, and drug content of 98.65 ± 1.78%. Stress stability was performed was well observed in nanoemulsion formulation. Nanoemulgel evaluation results were as follows: pH 5-6 was desirable for topical application, hardness was 43 gm, and spreadability was 79 gm with in vitro release of nanoemulgel at 91.98% and permeation study at 13.67%. CONCLUSION: The in vivo studies demonstrated the growth of newer hair follicles and increased hair diameter and length in dutasteride-loaded nanoemulgel-treated alopecia animals compared to the marketed sample and testosterone-treated group. Provided with the same and long-term storage stability, the developed formulation is supposed to offer a good option for the topical administration of dutasteride in treating androgenic alopecia.

Characterizing the spatio-temporal distribution, detection, and prediction of aerosol atmospheric rivers on a global scale.

Aerosol Atmospheric Rivers (AARs) are elongated and narrow regions that carry high concentrations of aerosols (tiny particles suspended in the atmosphere) across large distances, exerting effects on both air quality and human health (Chakraborty et al., 2021, 2022). Monitoring and modeling these aerosols present distinct challenges due to their dynamic nature and complex interactions within the atmosphere. In this context, the present study detects and predicts the AARs using MERRA-2 reanalysis datasets with their seasonal climatology of key aerosol species, including Black Carbon (BC), Dust (DU), Organic Carbon (OC), Sea Salt (SS), and Sulphates (SU). The study employs an innovative Integrated Aerosol Transport (IAT) based AAR algorithm from 2015 to 2022. A total count of 44,020 BC AARs, 13,280 DU AARs, 21,599 OC AARs, 17,925 SS AARs, and 31,437 SU AARs were detected globally. The seasonal climatology of BC and OC AARs intensifies in areas such as the Amazon rainforest and Congo during AMJJAS (April-September) due to forest fires. Similarly, DU AARs are more frequent in regions near the Saharan desert, primarily around the equator during AMJJAS. SS AARs tend to predominate over the oceans, while SU AARs are predominantly found in the northern hemisphere, primarily due to higher anthropogenic emissions. Furthermore, convolutional autoencoder-based models were developed for key aerosol species, strengthening predictive accuracy by effectively capturing complex data relationships and delivering precise predictions for the last 5-time frames. During validation, the model evaluation parameters for image prediction such as the Structural Similarity Index ranged from 0.86 to 0.94, Peak Signal-to-Noise Ratio fluctuated between 1.14 and 42.25 dB, Root Mean Square Error varied from 2.39 to 296.4 mg/(m-sec), and Mean Square Error fell within the range of 1.55-17.22 mg/(m-sec). These collectively reflect image closeness, quality, dissimilarity, and accuracy in AAR prediction. This study demonstrates the effectiveness of advanced machine and deep learning models in predicting AARs, offering the potential for advanced forecasting and enhancing resilience in high-aerosol concentration regions.

Improving the Device Performance of CZTSSe Thin-Film Solar Cells via Indium Doping.

Cation incorporation emerges as a promising approach for improving the performance of the kesterite Cu2ZnSn(S,Se)4 (CZTSSe) device. Herein, we report indium (In) doping using the chemical bath deposition (CBD) technique to enhance the optoelectronic properties of CZTSSe thin-film solar cells (TFSCs). To incorporate a small amount of the In element into the CZTSSe absorber thin films, an ultrathin (<10 nm) layer of In2S3 is deposited on soft-annealed precursor (Zn-Sn-Cu) thin films prior to the sulfo-selenization process. The successful doping of In improved crystal growth and promoted the formation of larger grains. Furthermore, the CZTSSe TFSCs fabricated with In doping exhibited improved device performance. In particular, the In-CZTSSe-2-based device showed an improved power conversion efficiency (PCE) of 9.53%, open-circuit voltage (Voc) of 486 mV, and fill factor (FF) of 61% compared to the undoped device. Moreover, the small amount of In incorporated into the CZTSSe absorber demonstrated reduced nonradiative recombination, improved carrier separation, and enhanced carrier transport properties. This study suggests a simple and effective way to incorporate In to achieve high efficiency and low Voc loss.

Multivariate statistical analysis to assess the surface water quality of a snow and glacier-fed river: A case from Alaknanda River basin.

The water quality of Himalayan rivers has declined due to human activities, untreated effluent discharge, and poor sewage and drainage systems. The current study aimed to assess the water quality of these rivers using multivariate statistical analysis throughout four seasons. The analyses of 44 surface water samples taken during the monsoon, winter, spring, and summer seasons are well within the ranges acceptable for drinking and domestic use after the sedimentation. The suspended soils and turbidity are highly correlated and affect the water quality index (WQI). The WQI of headwater streams is good during low water flow seasons and poor during high water flow seasons. This is due to the number of melting glaciers and suspended solids/turbidity. Principal component analysis shows that in all the seasons, human activities such as road-cutting projects across the river and natural causes such as intense rainfall and melting of moraine-filled glaciers both impact the WQI. The findings of this study provide important information for future research and policy decisions aimed at improving the water quality of the Himalayan rivers.

Osmolyte induced protein stabilization: modulation of associated water dynamics might be a key factor.

The mechanism of protein stabilization by osmolytes remains one of the most important and long-standing puzzles. The traditional explanation of osmolyte-induced stability through the preferential exclusion of osmolytes from the protein surface has been seriously challenged by the observations like the concentration-dependent reversal of osmolyte-induced stabilization/destabilization. The more modern explanation of protein stabilization/destabilization by osmolytes considers an indirect effect due to osmolyte-induced distortion of the water structure. It provides a general mechanism, but there are numerous examples of protein-specific effects, i.e., a particular osmolyte might stabilize one protein, but destabilize the other, that could not be rationalized through such an explanation. Herein, we hypothesized that osmolyte-induced modulation of associated water might be a critical factor in controlling protein stability in such a medium. Taking different osmolytes and papain as a protein, we proved that our proposal could explain protein stability in osmolyte media. Stabilizing osmolytes rigidify associated water structures around the protein, whereas destabilizing osmolytes make them flexible. The strong correlation between the stability and the associated water dynamics, and the fact that such dynamics are very much protein specific, established the importance of considering the modulation of associated water structures in explaining the osmolyte-induced stabilization/destabilization of proteins. More interestingly, we took another protein, bromelain, for which a traditionally stabilizing osmolyte, sucrose, acts as a stabilizer at higher concentrations but as a destabilizer at lower concentrations. Our proposal successfully explains such observations, which is probably impossible by any known mechanisms. We believe this report will trigger much research in this area.

Deciphering the Patterns of Dual Primary Cases Registered at the Hospital-Based Cancer Registry: First Experience from Rural Cancer Center in North India.

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary.

Understanding the intricacy of protein in hydrated deep eutectic solvent: Solvation dynamics, conformational fluctuation dynamics, and stability.

Deep eutectic solvents (DESs) are potential biocatalytic media due to their easy preparation, fine-tuneability, biocompatibility, and most importantly, due to their ability to keep protein stable and active. However, there are many unanswered questions and gaps in our knowledge about how proteins behave in these alternate media. Herein, we investigated solvation dynamics, conformational fluctuation dynamics, and stability of human serum albumin (HSA) in 0.5 Acetamide/0.3 Urea/0.2 Sorbitol (0.5Ac/0.3Ur/0.2Sor) DES of varying concentrations to understand the intricacy of protein behaviour in DES. Our result revealed a gradual decrease in the side-chain flexibility and thermal stability of HSA beyond 30 % DES. On the other hand, the associated water dynamics around domain-I of HSA decelerate only marginally with increasing DES content, although viscosity rises considerably. We propose that even though macroscopic solvent properties are altered, a protein feels only an aqueous type of environment in the presence of DES. This is probably the first experimental study to delineate the role of the associated water structure of the enzyme for maintaining its stability inside DES. Although considerable effort is necessary to generalize such claims, it might serve as the basis for understanding why proteins remain stable and active in DES.

Exploring temperature dynamics in Madhya Pradesh: a spatial-temporal analysis.

Understanding the dynamics of temperature trends is vital for assessing the impacts of climate change on a regional scale. In this context, the present study focuses on Madhya Pradesh state in Central Indian region to explore the spatial-temporal distribution patterns of temperature changes from 1951 to 2021. Gridded temperature data obtained from the Indian Meteorological Department (IMD) in 1° × 1° across the state are utilised to analyse long-term trends and variations in temperature. The Mann-Kendall (MK) test and Sen's slope (SS) estimator were used to detect the trends, and Pettitt's test was utilised for change point detection. The analysis reveals significant warming trends in Madhya Pradesh during the study period during specific time frames. The temperature variables, such as the annual mean temperature (Tmean), maximum temperature (Tmax), and minimum temperature (Tmin), consistently increase, with the most pronounced warming observed during winter. The trend analysis reveals that the rate of warming has increased in the past few years, particularly since the 1990s. However, Pettitt's test points out significant changes in the temperature, with Tmean rising from 25.46 °C in 1951-2004 to 25.78 °C in 2005-2021 (+0.33 °C), Tmax shifting from 45.77 °C in 1951-2010 to 46.24 °C in 2011-2021 (+0.47°C), and Tmin increasing from 2.65 °C in 1951-1999 to 3.19 °C in 2000-2021 (+0.46 °C). These results, along with spatial-temporal distribution maps, shed important light on the alterations and variations in monthly Tmean, Tmax, and Tmin across the area, underlining the dynamic character of climate change and highlighting the demand for methods for adaptation and mitigation.

Association of a novel begomovirus species with fenugreek yellow vein disease in India.

BACKGROUND: Fenugreek (Trigonella foenum-graecum L.) is an annual medicinal and spice crop belonging to the family Fabaceae. The occurrence of a yellow vein disease was recorded in fenugreek in Jodhpur (India) in 2022. The infection of begomoviruses in legume crops results in significant yield loss and major economic loss. The current study reports an association of a novel begomovirus species associated with yellow vein disease in Fenugreek. METHODS AND RESULTS: In symptomatic fenugreek plants, geminivirus-like particles were visible under a transmission electron microscope. Further, nucleotide sequence analysis of the rolling circle amplified product revealed 2743 nucleotide DNA-A genome with close relatedness to French bean leaf curl virus (88.21%) and Senna leaf curl virus (87.63%). It was proposed as a new begomovirus species, Fenugreek yellow vein Rajasthan virus. The genome organization suggested the presence of a typical nonanucleotide sequence along with 7 ORFs in DNA-A. A possible recombination event took place in the coat protein (V1) region with Pedilanthus leaf curl virus and Chilli leaf curl virus as major and minor parents. The recombinant virus poses possible threats to several other legume crops. To the best of our knowledge, this is the first report of the association of FeYVRaV with fenugreek yellow vein disease from northwestern India. CONCLUSIONS: In conclusion, the presence of a novel begomovirus species associated with yellow vein disease in fenugreek is alarming and needs further studies on its infectivity to prevent its spread to legume crops.

Evaluating the Effect of Different Intra-Orifice Barriers and Various Bleaching Agents on the Fracture Resistance of Teeth After the Walking Bleach Procedure: An In Vitro Study.

Objective This study aimed to evaluate the effect of three different commercially available intra-orifice barriers and bleaching agents on root canal-treated teeth. Materials and methods Forty-five freshly extracted single-rooted incisors, canine, and premolars were collected and stored in 10% formalin. Root canal procedures were performed on the extracted teeth and these were classified into three groups and three subgroups (n=5). Group 1: resin-modified glass ionomer cement (RMGIC); placed at the level of cemento-enamel junction (CEJ) and cured for 20 seconds. Group 2: BiodentinTM (Septodont Ltd., Saint Maur des Fausse´s, France); powder and liquid were mixed according to the manufacturer's instructions and placed at the level of CEJ, and waited for 15 minutes to set. Group 3: bulk-fill composite; placed at the level of CEJ. Group A was treated with 35% carbamide peroxide (Ultradent Opalescence 35% PF regular). Group B was bleached with 35% hydrogen peroxide (Pola Office). Group C, which was the control group, was treated with distilled water. The bleaching procedure was repeated once every seven days for a period of three weeks. After bleaching, every sample was sectioned 2 mm above the level of CEJ to remove the crown. Auniversal testing machine (UTM) was used for the evaluation of the fracture resistance of teeth. Data were analyzed for significance by using analysis of variance (ANOVA) and further pair-wise comparison was performed by pos-hoc analysis. The level of significance was set at p<0.05 Results There was a significant difference between the fracture resistance of the three materials when bleached using distilled water (p<0.05). The fracture resistance of Group 3 was significantly greater than that of Group 2 and Group 1 (p<0.05). The difference in the fracture resistance between Group 1 and Group 2 was nonsignificant (p>0.05). Conclusion Walking bleach performed via bleaching agents 35% carbamide peroxide and 35% hydrogen peroxide leads to a reduction in the fracture resistance of endodontically treated teeth; 35% hydrogen peroxide causes more fracture resistance reduction than carbamide peroxide of the same concentration. The presence of intra-orifice barriers leads to greater fracture resistance and reinforcement of endodontically treated teeth that undergo the walking bleach procedure. Bulk-fill composite can be used as an intra-orifice barrier with good fracture resistance.

Cell Voltage-Dependent Structural Dichotomy: Electrochemical C-H Acyloxylation and N-Acylation of 2H-Indazoles.

A simple and efficient electrochemical method that utilizes modulation of the cell voltage to cause structural alterations in 2H-indazole is introduced. This method enables the C-3 acyloxylation of 2H-indazole and promotes the transfer of the acyl group from C-3 to N-1, allowing the N-acylation of 2H-indazoles. Additionally, the application of the µ-electro flow reactor was demonstrated, showcasing its effectiveness in achieving gram-scale production of 3x within a short residence time.