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Enhancing crop productivity and their nutritional quality are the key components and primary focus of crop improvement strategy for fulfilling future food demand and improving human health. Grain filling and endosperm development are the key determinants of grain yield and nutritional quality. GRAIN WIDTH and WEIGHT2 ( GW2 ) gene encodes a RING-type E3 ubiquitin ligase and determines the grain weight in cereal crops. Here we report GW2 knockout (KO) mutants in Indica (var. MTU1010) through CRISPR/Cas9 genome editing. The endosperm of GW2 -KO mutant seed displays a thick aleurone layer with enhanced grain protein content. Further the loss of function of OsGW2 results in improved accumulation of essential dietary minerals (Fe, Zn, K, P, Ca) in the endosperm of rice grain. Additionally, the mutants displayed an early growth vigour phenotype with an improved root and shoot architecture. The hull morphology of GW2 -KO lines also showed improved, grain filling thereby promoting larger grain architecture. Together, our findings indicate that GW2 may serve as a key regulator of improved grain architecture, grain nutritional quality and an important modulator of plant morphology. The study offers a strategy for the development of improved rice cultivars with enriched nutritional quality and its possible implementation in other cereals as well.

The growing significance of superalloys like Hastelloy X, particularly in critical engineering sectors such as aerospace, chemical processing, and selective biomedical equipment (e.g., surgical instruments and medical tooling), underscores the need for advancements in their manufacturing processes. In today’s era of advanced manufacturing, it is crucial to develop machining systems that are both environmentally sustainable and cost-effective. To bridge the existing gap between economic, technological, and sustainability aspects in the machining of Hastelloy X, the present research aims to shed light on this critical interplay. Experimental investigations were conducted to evaluate the performance of various cooling techniques, including dry machining, minimum quantity lubrication (MQL), and cryogenic cooling using liquid nitrogen (LN₂) and carbon dioxide (CO₂). The results revealed that cryogenic cooling with LN₂ demonstrated superior performance across technological, sustainability, and economic metrics, outperforming other methods. Specifically, LN₂ cooling during the turning of Hastelloy X led to a reduction in tool wear and surface roughness by 21.11% and 25%, respectively, over dry machining conditions. These findings highlight the potential of advanced lubrication and cooling techniques to enhance sustainable manufacturing practices, reducing resource consumption while improving machining performance, particularly for industries involving difficult-to-machine superalloys.

Background The Janus kinase (JAK) and signal transduction and activation of transcription (STAT) signaling pathway is an attractive target in multiple cancers. Activation of the JAK-STAT pathway is important in both tumorigenesis and activation of immune responses. In diffuse large B-cell lymphoma (DLBCL), the transcription factor STAT3 has been associated with aggressive disease phenotype and worse overall survival. While multiple therapies inhibit upstream signaling, there has been limited success in selectively targeting STAT3 in patients. Antisense oligonucleotides (ASOs) represent a compelling therapeutic approach to target difficult to drug proteins such as STAT3 through of mRNA targeting. We report the evaluation of a next generation STAT3 ASO (AZD9150) in a non-Hodgkin’s lymphoma population, primarily consisting of patients with DLBCL. Methods Patients with relapsed or treatment refractory lymphoma were enrolled in this expansion cohort. AZD9150 was administered at 2 mg/kg and the 3 mg/kg (MTD determined by escalation cohort) dose levels with initial loading doses in the first week on days 1, 3, and 5 followed by weekly dosing. Patients were eligible to remain on therapy until unacceptable toxicity or progression. Blood was collected pre- and post-treatment for analysis of peripheral immune cells. Results Thirty patients were enrolled, 10 at 2 mg/kg and 20 at 3 mg/kg dose levels. Twenty-seven patients had DLBCL. AZD9150 was safe and well tolerated at both doses. Common drug-related adverse events included transaminitis, fatigue, and thrombocytopenia. The 3 mg/kg dose level is the recommended phase 2 dose. All responses were seen among DLBCL patients, including 2 complete responses with median duration of response 10.7 months and 2 partial responses. Peripheral blood cell analysis of three patients without a clinical response to therapy revealed a relative increase in proportion of macrophages, CD4+, and CD8+ T cells; this trend did not reach statistical significance. Conclusions AZD9150 was well tolerated and demonstrated efficacy in a subset of heavily pretreated patients with DLBCL. Studies in combination with checkpoint immunotherapies are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT01563302 . First submitted 2/13/2012.

Diurnal variation of convective storms (CSs) during monsoon season and associated physical mechanisms are significantly important for accurate forecast of short-time and extreme precipitation. The diurnal cycle of CSs is investigated using ground-based X-band radar, Tropical Rainfall Measuring Mission Precipitation Radar, and reanalysis data during the summer monsoon (June–September of 2014) over complex mountain terrain of Western Ghats, India. Diurnally, CSs show a bimodal distribution in the coastal areas, but this bimodality became weak along the upslope regions and on the mountain top. The first occurrence mode of CSs is in the afternoon–evening hours, while the second peak is in the early-morning hours. The diurnal cycle’s intensity varies with location, such that it reaches maximum in the afternoon–evening hours and early morning on the mountain top and coastal areas, respectively. Two possible mechanisms are proposed for the observed diurnal variation in CSs (a) the radiative cooling effect and (b) the surface wind convergence induced by the interaction between land-sea breeze, local topography and large-scale monsoon winds. It is also observed that the CSs developed on the mountain top during afternoon–evening hours are deeper than those along the coast. The higher moisture in the lower- and mid-troposphere, higher instability and strong upward motion facilitate deeper CSs during afternoon–evening hours.

The Indian summer monsoon trough (MT) is a dynamically active region of the quasi-stationary feature extending from north-western India towards the Bay of Bengal (BoB). The eastern rim of the MT (EMT) is modulated by the embedded synoptic-scale monsoon low-pressure systems (LPSs) in north BoB. We examine the spatiotemporal variability of the convective storm (CS) in the EMT region, which lies along the pathway of LPSs. A Lagrangian-based objective-tracking method, Thunderstorm Identification, Tracking, Analysis, and Nowcasting (TITAN), was injected into Kolkata S-band radar observations of nine wet seasons (June–September, 2009–2017). CSs frequently occur near the onshore areas and is linked to the formation and propagation of LPSs in the BoB. By examining the relationship of CS top heights with reflectivity lapse rate and fractional volume of 40 dBZ or more, three vertical categories of CS have been identified as shallow (SCS) below 5 km, medium depth (MDCS), and deep CS (DCS). The land–ocean contrast in the spatial distribution of MDCS and DCS and the contoured frequency by altitude diagram shows continental convective vigor. Although short-lived smaller CSs account for most storms in EMT, the bulk of the precipitation (75 % ) contributed from the infrequent largest storms. A weak (strong) linkage between the precipitation flux and CS top (area-time integral) gives a clue on the importance of CS voluminous organization rather than the linkage of heaviest rainfall to tallest CS. While most CSs propagate inland following the mass-weighted mean winds, the largest CS propagate offshore steered by the mid-level wind at 700 hPa.

Cystic Fibrosis (CF) is a hereditary condition and can cause permanent respiration problems leading to degraded life quality. The most common variation leading to CF is the F508del variation. CF can cause damage to not just the lungs but also digestive system, pancreas, and other organs. CF decreases the life expectancy of the individuals affected with the constant fear of lung complications. The current methods of treatment include using a combination of drugs to manage the symptoms. The combination of drugs has many side effects and causes damage to other organs like liver, heart or kidneys. In this study, we aim to find a drug that can relieve the symptoms of CF. We began by creating a dataset of potential drug molecules, which was subsequently refined by removing harmful compounds through an ADMET scan. All these compounds were then docked to the mutated Cystic Fibrosis Transmembrane Regulator (CFTR) protein. The compounds with the best docking affinity were Galicaftor and Bamocaftor. A currently approved drug, Ivacaftor was selected as control for the 200 ns Molecular Dynamics (MD) Simulation. The simulation revealed that the CFTR protein remained more stable and compact when complexed with Bamocaftor, when compared to Ivacaftor and Galicaftor. Moreover, the MMPBSA free energy calculations revealed that the free energy of the CFTR-bamocaftor complex is the lowest compared to the other complexes. Our findings reveal the action of bamocaftor on CFTR protein with p.Phe508del variation. However, the absence of in-vivo or in-vitro studies is a limitation, and further experimental validation is necessary to confirm its efficacy and safety.

Bruxism is commonly considered a detrimental motor activity, potentially causing overload of the stomatognathic structures. The etiology of bruxism is unclear, but the condition has been associated with stress, occlusal disorders, allergies and sleep positioning. Due to its nonspecific pathology, bruxism may be difficult to diagnose. Unfortunately, very little data exists on the subject of a cause-and-effect relationship of bruxism to the point that expert opinions and cautionary approaches are still considered the best available sources for suggesting good practice indicators. The present paper reviewed current concepts on bruxism, etiology, diagnosis and management, underlining its effects on dental structures in an attempt to provide clinically useful suggestions based on scientifically sound data.

Summary Glyphosate is a popular, systemic, broad‐spectrum herbicide used in modern agriculture. Being a structural analog of phosphoenolpyruvate (PEP), it inhibits 5‐enolpyruvylshikimate 3‐phosphate synthase (EPSPS) which is responsible for the biosynthesis of aromatic amino acids and various aromatic secondary metabolites. Taking a lead from glyphosate‐resistant weeds, two mutant variants of the rice EPSPS gene were developed by amino acid substitution (T173I + P177S; TIPS‐OsEPSPS and G172A + T173I + P177S; GATIPS‐OsEPSPS). These mutated EPSPS genes were overexpressed in rice under the control of either native EPSPS or constitutive promoters (maize ubiquitin [ZmUbi] promoter). The overexpression of TIPS‐OsEPSPS under the control of the ZmUbi promoter resulted in higher tolerance to glyphosate (up to threefold of the recommended dose) without affecting the fitness and related agronomic traits of plants in both controlled and field conditions. Furthermore, such rice lines produced 17%–19% more grains compared to the wild type (WT) in the absence of glyphosate application and the phenylalanine and tryptophan contents in the transgenic seeds were found to be significantly higher in comparison with WT seeds. Our results also revealed that the native promoter guided expression of modified EPSPS genes did not significantly improve the glyphosate tolerance. The present study describing the introduction of a crop‐specific TIPS mutation in class I aroA gene of rice and its overexpression have potential to substantially improve the yield and field level glyphosate tolerance in rice. This is the first report to observe that the EPSPS has role to play in improving grain yield of rice.

Primary angiosarcoma of breast (PAB) is a very rare disease and it accounts for only 0.05% of all malignant breast tumors. We present the clinical radiological and pathological features, treatment given, and outcome of this rare disease in our institute in a period of 5 years, aiming at contributing to the knowledge of prognostic factors of this rare disease. We report a case of PAB treated at our hospital along with 2 more cases of PAB we found on retrospective analysis. The basic criterion for inclusion in the study was the presence of histopathologically confirmed primary angiosarcoma of the breast: graded into low (G1, G2) and high (G3) grades. Surgeons must be aware about its high systemic metastatic potential, atypical presentation, and diffuse nature of infiltration so that it will be diagnosed early, and undergo a margin negative excision with reconstruction after a proper metastatic evaluation.

Objective: The objective was to study the symptomatology of testicular torsion of patients operated in our hospital and their operative results in relation to the duration of symptoms. Materials and Methods: Data of all patients operated for acute scrotum at all ages over a 14 months' time were collected from hospital records. Symptomatology and operative results were studied. Results: Out of 101 consecutive scrotal explorations done in this time, 63.4% of all scrotal explorations were testicular torsion (n = 64). 22.8% were appendage torsion (n = 23) and 13.9% were epididymo-orchitis (n = 14). The peak age of testicular torsion was in the 11-15 years range and the left side is more common (65.6%). Symptoms of scrotal pain (92.2%), abdominal pain (18.8%), nausea/vomiting (18.8%), fever (9.4%), and urinary symptoms (3.1%) were seen in decreasing order of frequency. Among acute scrotum patients who had symptoms of nausea/vomiting or abdominal pain, testicular torsion was found to be significantly higher compared to those who did not have these symptoms (χ2 = 0.044, P < 0.05). In all cases presented within 6 h of symptom onset, testicles were saved and salvage rates reduced with delay in presentation. The testicular salvage rates were 28.1% (18 out of 64 torsions). Patients below 18 years had more chance of going for orchiectomy than others (75% vs 66.7%). Patients who presented after 24 h had a statistically significantly lower salvage rate of 7.7% compared to those who presented within 24 h duration, 52.2%(χ2 = 0.001, P < 0.05). Those with orchiopexy had a median duration of symptom of 6.5 h and the same for orchiectomy patients were 72 h. Our median symptom duration for testicular torsion was 36 h and it is higher than many other countries. Conclusions: Delay in presentation to the health-care facility is the major cause of poor salvage rates in the state and its improvement requires public health interventions and health education.