The role of RIPK1 in chronic obstructive pulmonary disease.

Necroptosis has emerged as one of the crucial pathological processes involved in the regulation of cell death and inflammation in chronic obstructive pulmonary disease (COPD). Airway epithelial necroptosis is closely linked to COPD pathogenesis. Necroptotic lung cells can release damage-associated molecular patterns (DAMPs) that can initiate a robust inflammatory response. However, the underlying mechanism of necroptosis in COPD is still not clearly understood. Therefore, we aimed to explore the roles and mechanisms of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-mediated necroptosis in the regulation of inflammatory responses in COPD to provide insights into RIPK1-inhibitor drug discovery efforts and their therapeutic benefits in COPD.

Clinical and immunological predictors of post-rituximab paradoxical pemphigus flare: A prospective cohort study.

Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in detail. Objectives To evaluate the clinical and immunological predictors associated with post-rituximab paradoxical pemphigus flare. Materials and Methods This was a prospective cohort study including adult patients with pemphigus vulgaris or foliaceus who were treated with rituximab. Patients were administered 1000 mg of intravenous rituximab on days 0 and 14 (Rheumatoid arthritis (RA) protocol), with or without oral prednisolone and/or conventional immunosuppressive agents. Baseline clinical and immunological predictors of post-rituximab pemphigus flares were assessed. Results Fifty patients (mean age 40.44 ± 12.36 years) with a mean pemphigus disease area index (PDAI) score of 27.8 ± 15.48 were administered rituximab. Post-rituximab flare occurred in 10 (20%) patients after a mean of 14.1 ± 4.33 days after the first rituximab infusion. The mean baseline PDAI score (36.4 ± 11.7 vs. 25.6 ± 15.7, P = 0.02) and serum anti-Dsg1 levels (1216.8 ± 850.1 vs. 592 ± 562.12 RU/mL, P = 0.03) were statistically significantly higher in patients experiencing a flare. Using ROC-curve analysis, a PDAI score of 328 (OR 8.3, 95% CI 1.5-44.7) was 80% sensitive and 67.5% specific in predicting post-rituximab flare, while serum anti-Dsg1 level of 31137.78 RU/ml had a sensitivity of 60% and specificity of 85%. There was no significant difference in terms of affected body surface area, type of pemphigus, starting prednisolone dose, oral immunosuppressive adjuvant, serum anti-Dsg3, serum anti-AchRM3, and peripheral CD19+ B cell population. Limitations Our study is limited by a relatively small sample size. Immunological factors were not evaluated at the time of pemphigus flare. Though these unexpected pemphigus flares are likely to be associated with rituximab infusion, the possibility of spontaneous disease exacerbation cannot be entirely excluded. Conclusions Patients with more severe pemphigus or high serum anti-Dsg1 are at risk of post-rituximab paradoxical flare, and may benefit from rituximab administration under close monitoring.

Diagnostic accuracy of International System for Reporting Serous Fluid Cytopathology: A systematic review and meta-analysis in malignancy diagnosis.

This study conducts the first meta-analysis to assess the aggregated risk of malignancy associated with each category of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) for reporting serous effusion cytology, while also evaluating diagnostic accuracy. PubMed/MEDLINE and Embase were systematically searched using the keywords "(pleural, peritoneal, and pericardial effusions) AND (serous effusion cytology) OR (International System for Reporting Serous Fluid Cytopathology)". Articles underwent risk of bias assessment using the QUADAS-2 tool. After excluding inadequate samples, a meta-analysis determined sensitivity and specificity for different cutoff points, including "atypical considered positive," "suspicious of malignancy considered positive," and "malignant considered positive." Summary receiver operating characteristic curves assessed diagnostic accuracy, and the diagnostic odds ratio was pooled. Sixteen retrospective cross-sectional studies, totaling 19,128 cases, were included. Sensitivity and specificity for the "atypical and higher risk categories" considered positive were 77% (95% confidence interval [CI], 68%-84%) and 95% (95% CI, 93%-97%) respectively. For the "suspicious for malignancy and higher risk categories" considered positive, sensitivity and specificity were 57% (95% CI, 49%-65%) and 100% (95% CI, 99%-100%) respectively. Sensitivity and specificity for the "malignant" category considered positive for malignancy were 70% (95% CI, 60%-77%) and 99% (95% CI, 98%-99%), respectively. The pooled area under the curve ranged from 85% to 89.5% for each cutoff. This meta-analysis underscores the ISRSFC's accuracy in reporting serous fluid cytology. It emphasizes the diagnostic importance of the "suspicious" and "malignant" categories in identifying malignancy, and the role of the "benign" category in ruling out malignancy.

Morita-Baylis-Hillman Spirannulation under Phosphine- and Anion-Binding Catalysis.

We introduce an advancement in Morita-Baylis-Hillman (MBH) chemistry that provides access to α-spirannulated enones. The treatment of enone-tethered azaarenium salts with catalytic amounts of organophosphines provides spiroindenyl dihydropyridines. It represents the α-spirannulation of enones via an intramolecular MBH (IMBH) reaction utilizing dual phosphine- and anion-binding catalysis. The IMBH adducts were subjected to several post-synthetic modifications to access highly functionalized molecules.

Role of Platelet-rich Plasma in Unexplained Recurrent Implantation Failure - A Systematic Review and Meta-analysis of Randomised Control Trials.

Background: Recurrent implantation failure (RIF) is a challenging clinical situation and various strategies have been tried to improve the pregnancy rate in RIF. Platelet-rich plasma (PRP), which is obtained from the autologous blood samples of a person and is multiple times richer in platelets and other growth factors helps improve endometrial receptivity. Objective: This study has been conducted to summarise the evidence and quality of evidence available so far regarding the role of PRP in cases of unexplained RIF. Materials and Methods: An electronic database search for randomised clinical trials comparing PRP against routine care in women with unexplained RIF was performed on PubMed, EMBASE, SCOPUS and Cochrane Central. Two independent reviewers conducted a literature search and retrieved data using the predefined eligibility criteria. Bias assessment was done using the Cochrane Collaboration Network Risk of Bias Tool version 2. The quality of evidence was determined and a summary of the findings table was prepared for individual outcomes using GRADEpro software. Results: We identified 1146 records, and after removing duplicates, 531 records were screened. Out of these, 22 studies reached full-text screening and nine studies were included in the final review. We are uncertain about the effect of PRP due to the very low quality of evidence and we have little confidence that the administration of PRP had any significant effect on improving the live birth rate in women with RIF (odds ratio [OR]: 7.32, 95% confidence interval [CI]: 4.54-11.81, I2 = 40%). Similarly, the quality of evidence was low for the clinical pregnancy rate, so we are uncertain if the administration of PRP had any significant effect on the clinical pregnancy rate (OR: 3.20, 95% CI: 2.38-4.28, I2 = 0%). Interpretation: The current review suggests that there may be some beneficial effects of PRP in women with RIF, but the quality of evidence is very low and we are uncertain of the benefit and have little confidence in these findings. Limitations: Limitations are the small sample size of most studies, a short follow-up period, non-uniformity in the definition of outcomes and very low quality of evidence. Registration: The protocol was registered on PROSPERO (CRD42021292209).

Gait Analysis and Functional Knee Scores in Primary Knee Osteoarthritis and Their Correlation with Progression of the Disease in the Indian Population.

Introduction: Osteoarthritis of the knee is a leading cause of disability and is a multi-factorial disease. Moreover, it is partly considered a mechanically driven disease in which higher abnormally disbursed forces play a prime role. With the progression of the disease, the gait function declines, so a comprehensive and objective evaluation of gait function would help in prognostic evaluation and management. Materials and Methods: This study included two groups: patients with primary knee osteoarthritis and a control group of healthy volunteers. Gait analysis and functional knee scores were evaluated for all the subjects. The KOOS score, temporal parameters excluding the step length, and spatial parameters excluding the stance phase percentage were evaluated for an individual as a whole. The KSS score, kinetic parameters, kinematic parameters, step length, and stance phase percentage were calculated for each knee separately. Each knee of the patient and controls was taken as 1 sample and categorized as per Kellgren-Lawrence score. An asymptomatic control group of subjects were included in group A. Symptomatic patients with KL grades 1, 2 were included in group M, and those with KL grades 3, 4 were included in group S. The kinetic and kinematic parameters and KSS score were compared among the three groups. Results: A total of 60 subjects were included of which 40 were patients and 20 were controls. In the control group, the age ranged from 22 to 48 years with a mean age of 28.6 years. In the patient group, the mean age was 60.3 years. Patients with knee osteoarthritis were significantly obese with slower walking speed, short stride length, longer stride time, and decreased cadence compared to the asymptomatic group. There was a significant difference in spatiotemporal parameters, functional scores, and kinetic and kinematic parameters among the groups. Conclusion: Various spatiotemporal, kinetic, and kinematic parameters like peak knee flexion angle, abduction/adduction angle, peak knee adduction moment, range of knee flexion, peak knee flexion, and gait deviation index along with functional scores varied significantly with the progression of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-024-01103-9.

Neuropsychological Rehabilitation for Epilepsy in India: Looking Beyond the Basics.

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.

Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Investigating temperature variability on antioxidative behavior of synthesized cerium oxide nanoparticle for potential biomedical application.

Cerium oxide nanoparticles (CNP) have garnered significant attention due to their versatile redox properties and wound-healing applications. The antioxidative nature of CNP is due to its ability to be oxidized and reduced, followed by the capture or release of oxygen which is used for scavenging reactive oxygen species (ROS). Herein, CNP is produced through a wet chemistry approach and its tunable redox property is tested across a range of temperatures. The synthesized CNP was observed to reveal the signature peak at 245 nm indicating a high Ce+3/Ce+4 ratio. Towards evaluating the redox antioxidative behavior, CNPs were subjected to a comprehensive analysis for superoxide dismutase mimetic analysis with riboflavin-mediated nitroblue tetrazolium scavenging assay. The results demonstrated that the redox activity of cerium oxide nanoparticles was strongly influenced by the different temperature ranges. Superoxide dismutase mimetic activity was observed to be reduced with a decrease in temperature as we moved from 4°C (80% activity) to -80°C (47% activity) at 1 mM conc of CNP. Similarly, the SOD mimetic activity increased with an increase in temperature from 40°C (72% activity) to 70°C (94% activity). Further, CNP was found to inhibit E. coli (gram+ve) and Enterobacter (gram-ve) beyond 70% simultaneously at 1 mM conc, indicating its potential application as a remarkable antimicrobial agent. CNP also inhibited the alpha-amylase activity up to the 60% at 1 mM conc suggesting its potential application in antidiabetic wound healing therapy. Overall, the CNP finds its application in mitigating the oxidative stress-related disorder exhibited by its high antioxidative, antimicrobial, and antidiabetic behavior.

Attitude of Indian nurses towards importance of families in nursing care: A cross-sectional study.

AIMS AND OBJECTIVE: To evaluate the attitudes of Indian nurses towards the importance of family involvement in nursing care and the association between nurse attitudes and sociodemographic characteristics. BACKGROUND: Involving the family in the care process is crucial for delivering family- and patient-centred care and ensuring the best possible patient outcomes. Nevertheless, published literature revealed that the nurses may lack clarity regarding the role of family members in the patient's care, which in turn hinders families' participation in care. DESIGN: Cross-sectional descriptive study. The STROBE checklist was used to report the present study. METHODS: A total of 203 Nurses participated in a prospective cross-sectional study between May 2022 and August 2022. They were recruited through convenience sampling from two tertiary care centres in India. A two-part questionnaire was used to gather the data; the first section contained questions for gathering sociodemographic information, and the second part contained the standardized FINC-NA scale. RESULTS: The mean age of the nurses was (28.08 ± 4.722) years, and their median professional experience was 2.5 (1-5.5) years. Nurses' attitude regarding family's importance in patient care was found to be significantly associated (p ≤ .05) with education level, marital status, religion and hometown region. CONCLUSION: In several items Indian nurses have positive attitudes towards family involvement in care but some of the lower scoring items can present opportunities for focused improvement. Continuing development programmes about family-centered care can constitute important strategies to improve the positive attitudes of nurses towards families in practice. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.

Neuroprotective responses of quercetin in regulation of biochemical, structural, and neurobehavioral effects in 28-day oral exposure of iron in rats.

BACKGROUND: Iron is one of the essential metals that functions as a cofactor in various biological cascades in the brain. However, excessive iron accumulation in the brain may lead to neurodegeneration and may show toxic effects. Quercetin, a pigment flavonoid compound, has been proven to be a potent antioxidant and anti-inflammatory that can inhibit lipid peroxidation during metal-induced neurotoxicity. Although iron-induced neuroinflammation and neurodegeneration have been reported in many studies, but the proof for its exact mechanisms needs to be explored. PURPOSE: The key target of the study was to explore the neuroprotective effect of quercetin after oral exposure of iron in rats and explore its underlying molecular mechanisms. RESULTS: The outcomes of the study have shown that oral exposure to ferrous sulfate may modulate behavioral paradigms such as locomotor activity, neuromuscular coordination, and increased anxiety level. The pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), apoptotic protein (caspase 3), beta-amyloid and phosphorylated tau were found to be increased on iron exposure. Also, the expressions of ferritin heavy and light chain, BACE-1 and GFAP expressions were altered. These behavioral, structural, and biochemical alterations in the brain were significantly and dose-dependently reversed by treatment with quercetin. CONCLUSION: The current study provides a fundamental understanding of molecular signaling pathways, and structural proteins implicated in iron-induced neurotoxicity along with the ameliorative effects of quercetin.

Comparison of Outcomes following Vaginal Natural Orifice Transluminal Endoscopic Surgery and Laparoendoscopic Single-site Surgery in Benign Hysterectomy: A Systematic Review and Meta-analysis.

Gradually increasing interest in laparoscopic surgeries has led to the advent of various lesser invasive techniques in the form of vaginal natural orifice transluminal endoscopic surgery (vNOTES) and laparoendoscopic single-site (LESS) surgery. Very few studies have analyzed the advantages and disadvantages of vNOTES over LESS surgeries in hysterectomy. After a comprehensive search, full texts of relevant manuscripts were obtained to assess eligibility for recruitment. A comprehensive meta-analysis was subsequently performed to compare the outcomes of vNOTES and LESS in hysterectomy, and forest plots were constructed. Four articles were rendered for review (three retrospective cohort studies and one randomized controlled trial). Three studies showed lesser postoperative pain in vNOTES compared to LESS. In one study, postoperative vaginal pain was higher in vNOTES due to additional suture between uterine artery and vaginal wall. The meta-analysis concluded that vNOTES could be better alternative to LESS hysterectomies. However, further large multicentric randomized trials are required for the standardization of the surgical method.

Serum anti-Müllerian hormone: A potential biomarker for polycystic ovary syndrome.

BACKGROUND OBJECTIVES: Polycystic ovary syndrome (PCOS) is characterized by chronic ovulatory dysfunction, hyperandrogenism and polycystic ovary morphology (PCOM). Although hyperandrogenism is one of the major features of PCOS, it is rarely observed in southeast Asia. Recently, however, there has been growing evidence on association of anti-Müllerian hormone (AMH) with PCOS. The objective of this study was to investigate the diagnostic potentials of AMH in PCOS individuals. METHODS: This case-control study included a total of 131 women with PCOS and 49 healthy controls who were enrolled after the exclusion of secondary causes of PCOS. Serum AMH was measured using an ultra-sensitive AMH ELISA kit in addition to other diagnostic biomarkers. Statistical analyses was carried out using the Student's t test, Wilcoxon rank-sum test, receiver operating characteristic (ROC) curve analysis, Spearman's rank correlation test and multivariable binary logistic regression analysis. RESULTS: The median AMH values were 8.5 ng/ml and 2.5 ng/ml in the study group and controls, respectively ( P <0.001). The normal cutoff value of 4.1 ng/ml for AMH was derived from ROC curve analysis. With a 4.1 ng/ml cut-off value, high levels of AMH was found in about 84 per cent of PCOS cases. However, no significant difference in AMH level was noted between age groups (<20 vs . ≥20 yr), body mass index (BMI) (<25 vs . ≥25 kg/m 2 ) and PCOM types. The area under the ROC curve (AUC) for AMH yielded diagnostic range values. In total PCOS cases, AUC was 0.93 (95% CI: 0.88 and 0.96), and in phenotype A PCOS cases, AUC was 0.96 (95% CI: 0.91 and 0.98). The correlation test also showed no association with BMI, the FG score, PCOM, free androgen index, androstenedione, dehydroepiandrosterone sulphate and luteinizing hormone. However, a weak correlation was observed with testosterone in total PCOS cases and with DHT as well as age in phenotype A PCOS cases. The prediction model for PCOS using multivariable binary logistic regression analysis showed AMH as the best marker. INTERPRETATION CONCLUSIONS: The results of this study suggest that AMH can be considered as the most promising biomarker in PCOS women, particularly with phenotype A and phenotype D.

Malarial Antibodies and Endemicity: Does It Affect SARS-CoV-2 Severity and Outcomes?

Background India has a disproportionately lower rate of coronavirus disease 2019 (COVID-19) severe disease and lower death rates with respect to other parts of the world. It has been proposed that malaria-endemic countries such as India are relatively protected against severe COVID-19 disease and deaths. Methods This was a cross-sectional, analytical, observational study conducted from August 2020 to July 2021 at a tertiary care COVID-19-designated center in New Delhi, India. It aimed to study the association between antimalarial antibody levels and COVID-19 disease severity and outcomes. Results One hundred forty-six patients were included in the final analysis. The mean (standard deviation {SD}) age of the study population was 44.6 (17.2) years, and there were 85 (58.2%) males. Sixty-five patients had mild disease, 14 patients had moderate disease, and 67 patients had severe disease at the time of enrolment in the study. Forty-six patients expired during the hospital stay. For the antimalarial antibody, there was a statistically significant difference between mild and moderate (p=0.018), mild and severe (p=0.016), and mild and combined moderate and severe diseases (p=0.013). However, there was no difference between the patients who survived and those who did not. Conclusion Antimalarial antibody levels may not be associated with the outcomes of COVID-19 during hospital stay. However, this study has provided some insights into the relationship between the severity and outcomes of COVID-19 and the levels of antimalarial antibodies.

Rh(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-triazoles with Quinolones and Isoquinolones.

Herein, we developed an efficient approach to access biologically relevant 2-aminoquinolines and 1-aminoisoquinolines from readily available N-sulfonyl-1,2,3-triazoles and 2-quinolones or 1-isoquinolones. This transformation involves the selective O-H insertion of these derivatives onto the in situ generated Rh-azavinyl carbenes (Rh-AVC) followed by rearrangement. The reaction proceeds smoothly under operationally simple conditions and the protocol was found to be scalable.

Dendritic reorganization in the hippocampus, anterior temporal lobe, and frontal neocortex of lithium-pilocarpine induced Status Epilepticus (SE).

Status Epilepticus (SE) is a distributed network disorder, which involves the hippocampus and extra-hippocampal structures. Epileptogenesis in SE is tightly associated with neurogenesis, plastic changes and neural network reorganization facilitating hyper-excitability. On the other hand, dendritic spines are known to be the excitatory synapse in the brain. Therefore, dendritic spine dynamics could play an intricate role in these network alterations. However, the exact reason behind these structural changes in SE are elusive. In the present study, we have investigated the aforementioned hypothesis in the lithium-pilocarpine treated rat model of SE. We have examined cytoarchitectural and morphological changes using hematoxylin-eosin and Golgi-Cox staining in three different brain regions viz. CA1 pyramidal layer of the dorsal hippocampus, layer V pyramidal neurons of anterior temporal lobe (ATL), and frontal neocortex of the same animals. We observed macrostructural and layer-wise alteration of the pyramidal layer mainly in the hippocampus and ATL of SE rats, which is associated with sclerosis in the hippocampus. Sholl analysis exhibited partial dendritic plasticity in apical and basal dendrites of pyramidal cells as compared to the saline-treated weight-/age-matched control group. These findings indicate that region-specific alterations in dendritogenesis may contribute to the development of independent epileptogenic networks in the hippocampus, ATL, and frontal neocortex of SE rats.

Bio-oil and biochar production from Ageratum conyzoides using triple-stage hydrothermal liquefaction and utilization of biochar in removal of multiple heavy metals from water.

Production of low-cost biomass and its utilization for producing cost effective and eco-friendly bioenergy as well as for removing heavy metals from water can be explored as an approach to meet the sustainable development goals. In light of the above-mentioned study, hydrothermal liquefaction (HTL) of Billy goat weed (BGW; Ageratum conyzoides) was carried out to produce bio-oil. In addition, the residual biochar from the HTL process was activated to obtain Act-BC and was further modified to produce MnO2-loaded biochar (Act-BC@MnO2-25%). The HTL of BGW was done at three different temperatures, i.e., 250 °C, 350 °C and 450 °C in a high-pressure batch reactor to maximize the bio-oil yield. Also, two different HTL methods i.e., single-stage HTL and triple-stage HTL of BGW were compared and discussed in detail. The bio-oil obtained via the triple-stage HTL was rich in carbon, hydrogen, and nitrogen. It also showed a higher heating value (HHV) and bio-oil yield (46%) than the single-stage. The residual biochar obtained at 450 °C (Act-BC) and MnO2 modified (Act-BC@MnO2-25%) were then tested to adsorb multiple heavy metal (i.e., Pb(II), Cd(II), Cu(II), and Ni(II)) from water. The kinetics data obtained from the adsorption experiment with Act-BC@MnO2-25% were well fitted to PSO kinetics model. The isotherm data were well aligned with the Langmuir model; the adsorption capacity of Act-BC@MnO2-25% was estimated to be 198.70 ± 11.40 mg g-1, 93.70 ± 6.60 mg g-1, 78.90 ± 7.20 mg g-1 and 30.50 ± 2.10 mg g-1 for Pb(II), Cd(II), Cu(II), and Ni(II), respectively. Furthermore, Act-BC@MnO2-25% remained active for metal ions absorption even after six consecutive uses. The result obtained from this study clearly demonstrates that the triple-stage HTL of BGW is a promising technology to achieve both remediation of metal-contaminated water and production of bioenergy.

Monoclonal antibodies for the management of central nervous system diseases: clinical success and future strategies.

INTRODUCTION: Recombinant monoclonal antibodies (mAbs) are highly selective and effective biologicals with proven utility as therapeutics. mAbs have demonstrated substantial promise in the treatment of several central nervous system diseases. AREAS COVERED: Databases including PubMed and Clinicaltrials.gov were used to identify clinical studies of mAbs involving patients with neurological disorders. This manuscript reviews the current status and recent advances in the development and engineering of therapeutic blood-brain barrier (BBB)-crossing mAbs and their potential in treatment of central nervous system diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), brain tumors, and neuromyelitis optica spectrum disorder (NMSOD). In addition, the clinical implications of recently developed monoclonal antibodies are also discussed, along with the strategies to enhance their BBB permeability. The adverse events associated with the administration of monoclonal antibodies are also presented in the manuscript. EXPERT OPINION: There is growing evidence that supports the therapeutic utility of monoclonal antibodies in central nervous system and neurodegenerative diseases. Several studies have offered evidence of clinical efficacy in AD through use of anti-amyloid beta antibodies and anti-tau passive immunotherapy-based strategies. Additionally, ongoing research trials have produced promising findings for the treatment of brain tumors and NMSOD.

Access to Polysubstituted Furan Derivatives via Cascade Oxy-palladation and Hydrocarbofunctionalization of Unactivated Alkenes.

The development of an expedient strategy for the synthesis of biologically relevant multisubstituted furans is a much-desired yet challenging task. Herein, we report an efficient and versatile strategy involving two different pathways for the construction of diverse polysubstituted C3- and C2-substituted γ-furanyl carboxylic acid derivatives. The synthetic approach for C3-substituted furans involves intramolecular cascade oxy-palladation of alkyne-diols followed by the regioselective coordinative insertion of unactivated alkenes. In contrast, C2-substituted furans were obtained exclusively by performing the protocol in a tandem manner.