Akkermansia beyond muciniphila - emergence of new species Akkermansia massiliensis sp. nov.

The human gut commensal Akkermansia muciniphila is the most studied bacterial species within the Verrucomicrobiota phylum. It has been proposed as a beneficial next-generation probiotic for cardiometabolic and immune health. Efforts from various research groups have resulted in the recent discovery of new species and/or phylotypes of the genus Akkermansia. This highlighted the genetic and phenotypic diversity among the Akkermansia isolates, providing an opportunity to identify novel mechanisms pertaining to health benefits. Genetic diversity between strains warrants detailed investigation to determine beneficial Akkermansia strains. Akkermansia massiliensis sp. nov. has emerged as the second most prevalent Akkermansia species in the human gut, with unique properties and potential relevance for human health. In addition, indications of the co-existence of more than one Akkermansia phylotype or species in a subject are intriguing. These new discoveries pave the way for additional developments of effective and targeted Akkermansia species-based interventions to provide health benefits.

Impact of Cachexia on Chemotherapy Efficacy and Survival in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Pancreatic cancer (PC) is a significant cause of cancer-related mortality, with limited curative options and high rates of cachexia, a debilitating syndrome associated with poor prognosis. While previous research has linked sarcopenia to poor outcomes in PC, the correlation between cachexia and treatment outcomes remains underexplored. This meta-analysis aims to investigate the association between cachexia and overall survival and time to treatment failure in advanced PC patients undergoing first-line chemotherapy. METHOD: A systematic search of electronic databases was conducted following PRISMA guidelines. Eligible studies compared cachexic and non-cachexic PC patients, reporting outcomes of observed survival or time to treatment failure. Data extraction and analysis were performed using Comprehensive Meta-Analysis Version 3.3, employing random-effects models and sensitivity analyses to assess heterogeneity and bias. RESULTS: Seven observational studies involving 2834 PC patients were included. The incidence of cachexia was 45% (95% CI: 0.27-0.65), with a higher prevalence in East Asian populations. Cachexic patients experienced significantly earlier treatment failure (SDM: -2.22, 95% CI: -2.6 to -1.7, P = 0.0001) and higher mortality risk (HR: 2.02, 95% CI: 1.17-3.48, P = 0.011) compared to non-cachexic patients. Overall survival was lower in cachexic patients (SDM: -2.34, 95% CI: -3.7 to -0.90, P = 0.001), with considerable heterogeneity across studies. Meta-regression analysis revealed significant differences between countries but insignificant correlations with age. CONCLUSION: Cachexia is associated with reduced overall survival, early chemotherapy failure, and elevated mortality in advanced PC patients undergoing first-line chemotherapy. Recognition and management of cachexia are crucial for optimizing treatment outcomes and improving patient survival. Future research should focus on prospective studies to better understand the impact of cachexia on treatment response and develop tailored interventions to mitigate its adverse effects.

Pancreatic cancer (PC) presents a formidable challenge due to its limited treatment options and association with cachexia, a debilitating condition linked to poor prognosis. This meta-analysis investigates the relationship between cachexia and treatment outcomes in advanced PC patients undergoing first-line chemotherapy. Seven observational studies encompassing 2834 patients were analyzed, revealing a 45% incidence of cachexia, notably higher in East Asian populations. Cachexic patients exhibited earlier treatment failure and higher mortality risk compared to non-cachexic counterparts. Their overall survival was significantly reduced, although with notable heterogeneity across studies. Meta-regression analysis highlighted variations between countries but found no significant correlation with age. The findings underscore the importance of recognizing and addressing cachexia to optimize treatment outcomes and enhance patient survival. Future research should emphasize prospective studies to further elucidate cachexia's impact on treatment response and develop tailored interventions to alleviate its adverse effects.

Clinical Profile, Management, and Outcome of Posterior Urethral Valves in Children - Experience from a Tertiary Care Hospital.

Background: Posterior urethral valves (PUV) are the most common obstructive anomaly of the lower urinary tract in children. End-stage renal disease (ESRD) in 17% of the children is due to PUV. The present study helps know the spectrum of the disease, management options, and the outcome in these children. Methods: The present study is a descriptive type of study by review of medical records of all the children presented to the hospital from 2015 to 2019. Profile of PUV includes any abnormality in antenatal ultrasonography (USG), age at presentation, presenting complaints, general condition at the time of presentation, biochemical investigations like serum creatinine and electrolytes at admission, clinical progression during hospital stay and the type of intervention. Outcome variables studied were improvement in the stream and overall well-being of the child, renal function, recurrent urinary tract infections (UTIs). Follow-up period varied from 1 to 6 years. Results: A total of 73 patients were included in the study. The mean age of presentation was 3.4 years. The most common presenting complaints were poor urinary stream and dribbling of urine. Antenatal USG showed abnormality in 23 patients. Renal function was abnormal in 28 patients. Out of 73 patients, 51 underwent endoscopic ablation of valves, 19 underwent vesicostomy, and three patients underwent supravesical diversion. During the follow-up recurrent UTI was observed in 11 patients, 15 patients progressed to chronic kidney disease, and 15% of patients were hypertensive. Mortality in the present study was 4%. Conclusion: PUV includes a spectrum of diseases from mild form to lethal conditions. Early intervention by relieving obstruction may prevent or delay the ESRD; hence, timely intervention is necessary in these children.

A transition from enemies to allies: how viruses improve drought resilience in plants.

Global crop production is severely affected by environmental factors such as drought, salinity, cold, flood etc. Among these stresses, drought is one of the major abiotic stresses reducing crop productivity. It is expected that drought conditions will further increase because of the increasing global temperature. In general, viruses are seen as a pathogen affecting the crop productivity. However, several researches are showing that viruses can induce drought tolerance in plants. This review explores the mechanisms underlying the interplay between viral infections and the drought response mechanisms in plants. We tried to address the molecular pathways and physiological changes induced by viruses that confer drought tolerance, including alterations in hormone signaling, antioxidant defenses, scavenging the reactive oxygen species, role of RNA silencing and miRNA pathway, change in the expression of several genes including heat shock proteins, cellulose synthase etc. Furthermore, we discuss various viruses implicated in providing drought tolerance and examine the range of plant species exhibiting this phenomenon. By applying current knowledge and identifying gaps in understanding, this review aims to provide valuable insights into the complex dynamics of virus-induced drought tolerance in plants, paving the way for future research directions and practical applications in sustainable agriculture.

Anomalous drainage of inferior vena cava into left atrium associated with ostium secundum atrial septal defect: a case report.

Background: Anomalous drainage of inferior vena cava (IVC) into left atrium (LA) is a rare aetiology of cyanosis in adults. This condition may be associated with atrial septal defects, anomalous pulmonary venous drainage, and pulmonary arteriovenous fistulas. This case report presents an instance of anomalous drainage of IVC into LA, associated with ostium secundum atrial septal defect (ASD). It contributes to the existing literature by highlighting the diagnostic challenges associated with this anomaly, particularly during surgical intervention. Case summary: A 38-year-old male presented with a six-year history of exertional dyspnoea and episodic palpitation. Transthoracic echocardiography revealed a large secundum (ASD), the IVC draining into LA, a left superior vena cava, and mild mitral regurgitation. These findings were further confirmed by right and left heart catheterization and CT angiogram. The patient was referred to CTVS department for surgical correction. The post-operative course was uneventful. At a 1.4-year follow-up, the patient reported significant improvement in symptoms. Discussion: We present a case of anomalous drainage of IVC into LA, associated with ostium secundum ASD. An ASD co-occurs with this condition in ∼70% of the reported cases. This anomaly differs from a low or inferior vena caval secundum ASD, where a prominent Eustachian valve can cause blood shunting from the IVC to LA. If the surgeon is not vigilant, this can be mistaken for the inferior ASD rim, potentially leading to iatrogenic diversion of IVC blood to LA upon ASD closure, resulting in cyanosis. This case underscores the diagnostic and surgical challenges associated with this condition.

Possible roles of phytochemicals with bioactive properties in the prevention of and recovery from COVID-19.

Introduction: There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/beverages people consumed and the risk reduction of contracting COVID-19 and the recovery from COVID-19. Methods: We developed an online survey that asked the participants whether they contracted COVID-19, their symptoms, time to recover, and their frequency of eating various types of foods/beverages. The survey was developed in 10 different languages. Results: The participants who did not contract COVID-19 consumed vegetables, herbs/spices, and fermented foods/beverages significantly more than the participants who contracted COVID-19. Among the six countries (India/Iran/Italy/Japan/Russia/Spain) with over 100 participants and high correspondence between the location of the participants and the language of the survey, in India and Japan the people who contracted COVID-19 showed significantly shorter recovery time, and greater daily intake of vegetables, herbs/spices, and fermented foods/beverages was associated with faster recovery. Conclusions: Our results suggest that phytochemical compounds included in the vegetables may have contributed in not only preventing contraction of COVID-19, but also accelerating their recovery.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. METHODS: In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. RESULTS: Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). CONCLUSION: Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

A Case-based Guide for World Health Organization (WHO) Grade 2 Meningioma Radiosurgery and Radiation Therapy from The Radiosurgery Society.

PURPOSE: Meningiomas represent the most common primary tumor of the central nervous system. Current treatment options include surgical resection with or without adjuvant radiation therapy (RT), definitive RT, and observation. However, the radiation dose, fractionation, and margins used to treat patients with WHO grade 2 meningiomas, which account for approximately 20% of all meningiomas, are not clearly defined, and deciding on the optimal treatment modality can be challenging owing to the lack of randomized data. METHODS AND MATERIALS: In this manuscript, 3 cases of patients with WHO grade 2 meningiomas are presented with descriptions of treatment options after gross total resection, subtotal resection, and previous irradiation. Treatment recommendations were compiled from 9 central nervous system radiation oncology and neurosurgery experts from The Radiosurgery Society, and the consensus of treatment recommendations is reported. RESULTS: Both conventional and stereotactic RT are treatment options for WHO grade 2 meningiomas. The majority of prospective data in the setting of WHO grade 2 meningiomas involve larger margins. Stereotactic radiosurgery/hypofractionated stereotactic RT are less appropriate in this setting. Conventionally fractionated RT to at least 59.4 Gy is considered standard of care with utilization of preoperative and postoperative imaging to evaluate the extent of disease and possible osseous involvement. After careful discussion, stereotactic radiosurgery/hypofractionated stereotactic RT may play a role for the subset of patients who are unable to tolerate the standard lengthy conventionally fractionated treatment course, for those with prior RT, or for small residual tumors. However, more studies are needed to determine the optimal approach. CONCLUSIONS: This case-based evaluation of the current literature seeks to provide examples for the management of grade 2 meningiomas and give examples of both conventional and stereotactic RT.

Stereotactic Body Radiation Therapy for Primary Renal Cell Carcinoma: A Case-Based Radiosurgery Society Practice Guide.

Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.

PIK3/Akt/mTOR pathway alterations in metastatic castration-sensitive prostate cancer.

BACKGROUND: Alterations in the PIK3/Akt/mTOR pathway are commonly seen in metastatic castration-sensitive prostate cancer (mCSPC), however their role in outcomes is unknown. We aim to evaluate the prognostic significance as well as the genetic landscape of PIK3/Akt/mTOR pathway alteration in mCSPC. METHODS: Fourhundred and seventy-two patients with mCSPC were included who underwent next generation sequencing. PIK3/Akt/mTor pathway alterations were defined as mutations in Akt1, mTOR, PIK3CA, PIK3CB, PIK3R1, PTEN, TSC1, and TSC2. Endpoints of interests were radiographic progression-free survival (rPFS), time to development of castration resistant prostate cancer (tdCRPC), and overall survival (OS). Kaplan-Meier analysis was performed and Cox regression hazard ratios (HR) were calculated. RESULTS: One hundred and fifty-two (31.9%) patients harbored a PIK3/Akt/mTOR pathway alteration. Median rPFS and tdCRPC were 23.7 and 21.0 months in PIK3/Akt/mTOR altered compared to 32.8 (p = 0.08) and 32.1 months (p = 0.002) in wildtype tumors. On multivariable analysis PIK3/Akt/mTOR pathway alterations were associated with tdCRPC (HR 1.43, 95% CI, 1.05-1.94, p = 0.02), but not rPFS [Hazard ratio (HR) 1.20, 95% confidence interval (CI), 0.90-1.60, p = 0.21]. PIK3/Akt/mTOR pathway alterations were more likely to be associated with concurrent mutations in TP53 (40% vs. 28%, p = 0.01) and TMPRSS2-ERG (37% vs. 26%, p = 0.02) than tumors without PIK3/Akt/mTOR pathway alterations. Concurrent mutations were typically associated with shorter median times to rPFS and tdCRPC. DAVID analysis showed p53 signaling and angiogenesis pathways were enriched in PIK3/Akt/mTOR pathway altered tumors while beta-catenin binding and altered BRCA pathway were enriched in PIK3/Akt/mTOR pathway wildtype tumors. CONCLUSIONS: PIK3/Akt/mTOR pathway alterations were common in mCSPC and associated with poorer prognosis. The genetic landscape of PIK3/Akt/mTOR pathway altered tumors differed from wildtype tumors. Additional studies are needed to better understand and target the PIK3/Akt/mTOR pathway in mCSPC.

Phase Morphology Dependence of Ionic Conductivity and Oxidative Stability in Fluorinated Ether Solid-State Electrolytes.

Solid-state polymer electrolytes can enable the safe operation of high energy density lithium metal batteries; unfortunately, they have low ionic conductivity and poor redox stability at electrode interfaces. Fluorinated ether polymer electrolytes are a promising approach because the ether units can solvate and conduct ions, while the fluorinated moieties can increase oxidative stability. However, current perfluoropolyether (PFPE) electrolytes exhibit deficient lithium-ion coordination and ion transport. Here, we incorporate cross-linked poly(ethylene glycol) (PEG) units within the PFPE matrix and increase the polymer blend electrolyte conductivity by 6 orders of magnitude as compared to pure PFPE at 60 °C from 1.55 × 10-11 to 2.26 × 10-5 S/cm. Blending varying ratios of PEG and PFPE induces microscale phase separation, and we show the impact of morphology on ion solvation and dynamics in the electrolyte. Spectroscopy and simulations show weak ion-PFPE interactions, which promote salt phase segregation into-and ion transport within-the PEG domain. These polymer electrolytes show promise for use in high-voltage lithium metal batteries with improved Li|Li cycling due to enhanced mechanical properties and high-voltage stability beyond 6 V versus Li/Li+. Our work provides insights into transport and stability in fluorinated polymer electrolytes for next-generation batteries.

Prognostic value of residual SYNTAX score in patients with coronary artery disease undergoing percutaneous coronary intervention-cohort study.

Residual Syntax Score (RSS) is derived from Syntax Score to quantify the burden of residual coronary artery disease after percutaneous coronary intervention (PCI). As data is limited, we report predictive utility of Residual SYNTAX Score in relation to in hospital and 1 year mortality of the patients undergoing percutaneous coronary intervention (PCI).

α1-COP modulates plasmodesmata function through sphingolipid enzyme regulation.

Callose, a ß-1,3-glucan plant cell wall polymer, regulates symplasmic channel size at plasmodesmata (PD) and plays a crucial role in a variety of plant processes. However, elucidating the molecular mechanism of PD callose homeostasis is limited. We screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene was α1-COP, a member of the coat protein I (COPI) coatomer complex. We report that loss of function of α1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme PdBG2. This process is linked to the functions of ERH1, an inositol phosphoryl ceramide synthase, and glucosylceramide synthase through physical interactions with the α1-COP protein. Additionally, the loss of function of α1-COP alters the subcellular localization of ERH1 and GCS proteins, resulting in a reduction of GlcCers and GlcHCers molecules, which are key sphingolipid (SL) species for lipid raft formation. Our findings suggest that α1-COP protein, together with SL modifiers controlling lipid raft compositions, regulates the subcellular localization of GPI-anchored PDBG2 proteins, and hence the callose turnover at PD and symplasmic movement of biomolecules. Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.

Aerosol-PM2.5 Dynamics: In-situ and satellite observations under the influence of regional crop residue burning in post-monsoon over Delhi-NCR, India.

The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 µg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 µg/m³ (24 h) by 27-34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention.

Maleic acid crosslinked starch/polyvinyl alcohol blend films with improved barrier properties for packaging applications.

Incorporating starch, which is a potential biodegradable substitute for petroleum-based polymers, into conventional polymers is challenging owing to limitations in processability and weak-performing resulting materials. Herein, corn starch/polyvinyl alcohol (PVA) blend films (starch: PVA ratio of 50:50) were prepared via the solvent casting method using glycerol as a plasticizer and with varying concentrations of maleic acid as the crosslinking agent. Fourier transform infrared spectroscopy revealed the molecular interactions of the maleic acid crosslinker with the polymeric network of starch and PVA through an ester linkage. The properties of the films were strongly dependent on the maleic acid concentration. An increasing maleic acid concentration imparted hydrophobicity to the film; therefore, water swelling was significantly reduced, and water resistance was enhanced. The film containing 20 wt% maleic acid exhibited excellent barrier properties, with the lowest oxygen and water vapor transmission rates of 0.5 ± 0.2 cc/m2⋅day and 232.3 ± 5.4 g/m2⋅day, respectively. Moreover, the mechanical properties of the film improved with increasing crosslinking. This study demonstrates that the addition of maleic acid leads to an improvement in the overall performance of starch/PVA blend films. Therefore, maleic acid-crosslinked films can be used as barrier materials in food packaging applications.

Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergo metformin monotherapy. This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

C-Type LECTIN receptor-like kinase 1 and ACTIN DEPOLYMERIZING FACTOR 3 are key components of plasmodesmata callose modulation.

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

A Cross-Sectional Study of Acute Coronary Syndrome and Thyroid Profile: Dissecting the Relationship to Improve Patient Care.

INTRODUCTION: Thyroid-releasing hormones are pivotal in regulating cardiovascular (CVS) function and maintaining its hemodynamics and homeostasis. Even a minor alteration in thyroid function has an enormous implication on CVS morbidity and mortality. Moreover, hypothyroidism was found to be a potential menace for coronary artery disease (CAD). The objective of this study was to determine the role of thyroid-releasing hormones in patients suffering from acute coronary syndrome (ACS). METHODOLOGY: Among a cohort of 100 patients suffering with ACS, a complete history and clinical information followed by physical examination and electrocardiography were recorded. Blood samples were also collected to record the blood sugar levels i.e., fasting blood sugar (FBS), postprandial blood sugar (PPBS), and thyroid profile, including free thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), and reverse triiodothyronine (rT3). The data was analyzed using SPSS version 26 software (IBM Corp., Armonk, NY, USA). RESULT: The study identified alterations in the thyroid hormone levels in 27% of patients suffering from ACS. The prevalence of euthyroid sick syndrome was found to be 59.3%, while subclinical hypothyroidism and subclinical hyperthyroidism were reported among 18.5% and 14.8% of patients respectively. There was no significant difference found between males and females. The study illustrated a greater occurrence of aberrant thyroid hormone profiles among those aged 40-60 years. The ST-elevated myocardial infarction (STEMI) group had a statistically significant higher prevalence of an aberrant thyroid hormone profile compared to the non-ST-elevated myocardial infarction (NSTEMI) and unstable angina (UA) groups (p=0.02). A total of nine patients died with ACS and all of those had statistically significant low fT3 and TSH values while higher rT3 values (p<0.05). CONCLUSION: An atypical thyroid status has been found to elevate the likelihood of developing CAD and experiencing CVS mortality. This condition can impact ventricular function and serum cholesterol levels as well as heart rate and rhythm. Therefore, understanding this relationship could potentially lead to improved treatment strategies for individuals with ACS which will further prevent major CVS complications.

Biological wastewater treatment: a comprehensive sustainability analysis using life cycle assessment.

The research conducts a life cycle assessment (LCA) on wastewater treatment (WWT) methods-membrane bioreactor (MBR), soil biotechnology (SBT), and bio-electrochemical constructed wetlands (BCW)-in comparison with the conventional activated sludge process (ASP). Employing SimaPro v9.5 with a cradle-to-gate system boundary, the analysis utilizes the IMPACT 2002 + method, employing per cubic meter of treated wastewater as the functional unit. The analysis shows that SBT exhibits the lowest environmental impacts among the considered WWT methods. The global warming potential was 0.0996 kg CO2 eq. for SBT, 1.33 kg CO2 eq. for MBR, 0.131 kg CO2 eq. for BCW, and 0.544 kg CO2 eq. for ASP. BCW demonstrates a 75.91% decrease, while MBR exhibits a 144.48% increase compared to ASP. Notably, electricity consumption emerges as the primary contributor to environmental impact in MBR and ASP. The resource impact category varies with a 138.15% increase in MBR and an 83.41% decrease in SBT compared to ASP. Additionally, the research indicates that the high human health impact observed in MBR results mainly from increased carcinogens (0.00176 kg C2H3Cl eq.), non-carcinogens (0.01 kg C2H3Cl eq.), and ionizing radiation (3.34 Bq C-14 eq.). The findings underscore the importance of considering treatment efficiency and broader environmental implications in selecting WWT methods. As the world emphasizes sustainability, such LCA studies provide valuable insights for making informed decisions in wastewater management.