Deciphering the cell surface sugar-coating via Biochemical Pathways.

Cell surface components, specifically glycans, play a significant role in several biological functions like cell structure, crosstalk between cells, and eventual target recognition of the cells for therapeutics. The dense layer of glycans, i.e., glycocalyx, could differ in taxon, species, and cell type. Glycans are coupled with lipids and proteins to form glycolipids, glycoproteins, proteoglycans, and glycosylphosphatidylinositol-anchored proteins, making their study challenging. However, understanding glycosylation at the cellular level is vital for fundamental research and the advancement of glycan-targeted therapy. Among different pathways, metabolic glycan labelling uses the natural metabolic processes of the cell to introduce abiotic functionality into glycan residues. The Bertozzi group pioneered metabolic oligosaccharide engineering using glycan salvage pathways to convert monosaccharides with unnatural modifications. This eventually results in the probe becoming part of the complex cellular glycan structures via click chemistry using copper. On the other hand, the boronic acid-based probe can recognise carbohydrates in a single step without any chemical modification of the surface. This review discusses the significance of glycans as biomarkers for different diseases and the necessity to evaluate them in situ within the physiological environment. The review also discusses the prospect of this field and its potential applications.

Development of a bisphenol A based chemosensor for Al3+ and its application in cell imaging and plant root imaging.

Bisphenol A is a fluorophoric platform that is used to develop chemosensors for various species. Herein, we report a bisphenol A based Schiff-base molecule, 4,4'-(propane-2,2-diyl)bis(2-((E)-((2-hydroxy-5-methylphenyl)imino)methyl)phenol) (Me-H4L), as a selective chemosensor for Al3+. Among the several metal ions, it shows a significant increment in its fluorescence intensity (50 fold) at 535 nm in the presence of Al3+ ions. The enhanced fluorescence was attributed to the CHEFF mechanism and inhibition of CN isomerization. The limit of detection value of Me-H4L for Al3+ was determined to be 9.65 µM. Its quantum yield and lifetime increased considerably in the presence of the cation. Some theoretical calculations were performed to explain the interaction between Al3+ and the probe. Furthermore, Me-H4L was applied in cell imaging studies using animal cells and plant roots.

Burden of frailty and its correlates among the elderly: a cross-sectional study in a rural community of West Bengal.

Context: With the ageing of Indian society, providing a healthy life among older people is a public health precedence. Therefore, beforehand discovery and possible forestalment of frailty may help promote healthy ageing and dwindle the social, mental and financial burden of their families and caregivers. Aims: The study aimed to assess the proportion of frailty and its associated factors among the elderly aged 65 years and above in a rural community of West Bengal. Settings and Design: A community-based cross-sectional study was conducted among 270 elderlies selected from 15 villages out of a total 64 villages of Singur under the Hooghly District of West Bengal from January 2019 to February 2020. Materials and Methods: Cluster sampling technique was used. Data was collected using a pre-designed, pre-tested structured schedule including Fried frailty phenotype (FFP), geriatric depression scale short form (GDS 15) and mini nutritional assessment (MNA) tool. Statistical Analysis Used: Associated factors of frailty were assessed by univariate and multivariable logistic regression using SPSS version 16 software and MS Excel 2019. Results: The proportion of frailty was observed to be 23.7% and that of prefrailty 40.7%. Frailty was significantly associated with increasing age [AOR(CI) 1.2(1.1-1.3)], decreasing years of schooling [AOR(CI) 1.3(1.1-1.5)], loss of spouse [AOR(CI) 4.2(1.2-15.2)], financial dependency [AOR(CI) 19.3(2.7-139.0)], staying at home [AOR(CI) 16.3(2.7-98.2)], presence of anaemia [AOR(CI) 3.6(1.3-9.5)], at risk of malnutrition [AOR(CI) 6.5(1.9-22.3)], increasing number of falls in the last 1 year [AOR(CI) 4.3(1.2-15.6)], presence of 3 or more chronic diseases [AOR(CI) 154.7(12.1-1981.9)] and depression [AOR(CI) 8.3(2.5-27.0)]. Conclusion: The burden of frailty among the study population is relatively high. It's an intimidating situation that needs bettered screening provisions for early discovery with special stress on nutritive upliftment. Screening for depression should also be done regularly.

Room temperature ferroelectricity and an electrically tunable Berry curvature dipole in III-V monolayers.

Two-dimensional ferroelectric monolayers are promising candidates for compact memory devices and flexible electronics. Here, through first-principles calculations, we predict room temperature ferroelectricity in AB-type monolayers comprising group III (A = Al, In, Ga) and group V (B = As, P, Sb) elements. We show that their spontaneous polarization, oriented out-of-plane, ranges from 9.48 to 13.96 pC m-1, outperforming most known 2D ferroelectrics. We demonstrate an electric field tunable Berry curvature dipole and nonlinear Hall current in these monolayers. Additionally, we highlight their applicability in next-generation memory devices by forming efficient ferroelectric tunnel junctions, especially in InP, which supports high tunneling electroresistance. Our findings motivate further exploration of these monolayers for studying the interplay between the Berry curvature and ferroelectricity and for integrating these ferroelectric monolayers in next-generation electronic devices.

Boronic Acid-Linked Cell-Penetrating Peptide for Protein Delivery.

Studying functional protein delivery into live cells is important, ranging from fundamental research to therapeutics. Cell-penetrating peptides (CPPs) are known to deliver proteins with applauded efficacy and have gained importance for applications in protein therapeutics and exploration of versatile cellular mechanisms. The primary aim of the work is to design a CPP as a tool and delivery vehicle for macromolecules, including proteins. In this work, boronic acid-linked cyclic deca arginine (cR10) is reported as an efficient CPP that exhibited 3-fold higher delivery of chemically synthesized ubiquitin (Ub) than pristine cR10-linked Ub, examined with live U2OS cells. As a futuristic plan, an artificial intelligence machine learning-based rationale has been designed and proposed.

Deconstructing the sex gap in child undernutrition in India: Are Indian boys at elevated risk of anthropometric failure than the girls?

BACKGROUNDS & OBJECTIVES: The privileging of boys in immunization coverage, breastfeeding, and other child care practices in Indian patriarchal society raises questions about whether there are sex differences in the prevalence of undernutrition among children. This study evaluates the sex gap in the prevalence of Composite Index of Anthropometric Failure (CIAF) among Indian children from 2015-16 to 2019-21. Additionally, it seeks to identify the sex-specific determinants and persistent sex gap at national and subnational levels (social, economic, religious, and geopolitical regions) in anthropometric failure among the children from 2015-16 to 2019-21. MATERIALS AND METHODS: The study utilizes the 4th (2015-16) and 5th (2019-21) rounds of the National Family Health Survey data. Logistic regression models and the Fairlie decomposition technique were employed to explore the persistent and significant sex gap in the prevalence of CIAF, as well as the sex-specific determinants of CIAF among children in 2015-16 and 2019-21. RESULTS: The study reveals a significant sex gap (approximately 4%-points), with boy's disadvantage in the prevalence of CIAF from 2015-16 to 2019-21 at both the national and subnational levels (social, religious, socioeconomic groups, and geopolitical regions). The gap is more pronounced in the first year of life and decreases in later stages. A comparatively faster CIAF decline among girls from 2016 to 2021 has widened the sex gap in final year than the previous. Child, mother, household, community, and geographic backgrounds explains about 5%-6% of the sex gap in the prevalence of CIAF from 2015-16 to 2019-21. The remaining 94%-95% of the unexplained sex gap may be attributed to biological factors or other factors. Currently, a heightened boy's disadvantage in CIAF risk is observed in ST community, wealthiest families, and the northern India. CONCLUSION: The findings suggest a special attention for boys under 3 years to offset biological disadvantages like greater disease sensitivity and fragility compared to girls early on.

Review on Uric Acid Recognition by MOFs with a Future in Machine Learning.

Uric acid (UA) is produced from purine metabolism and serves as a prevalent biomarker for multiple diseases including cancer. Hyperuricemia or hypouricemia can cause multiple dysfunctions throughout the biological processes. Consequently, there is a pressing need for monitoring UA concentration in body fluid. While clinical methods are known, the availability of a point-of-care testing (PoCT) kit remains conspicuously absent. In the case of electrochemical recognition of UA, the oxidation potential of ascorbic acid closely aligns with that of UA and thus it hinders the detection process, which eventually may result in false positive signals. Several chemosensors are known in the field of supramolecular chemistry, and metal-organic frameworks (MOFs) are one of the best-performing contenders due to their robustness, stability, and versatile structures. In this review, we tried to unbox the up-to-date development of UA sensing by MOFs. We delve into the state of UA recognition by MOFs, exploring both electrochemical and fluorometric pathways and drawing comparisons with structurally similar probes like covalent organic frameworks (COFs) to understand/establish the advantages of MOFs specifically in UA sensing. In the absence of a PoCT kit, we have provided the conceptual outlook for designing a PoCT device termed a "Urimeter" via electrochemical operation. For the first time, we have proposed different methods of how UA sensing can be tied up with artificial intelligence and machine learning (AI-ML).

Undernutrition Among the Children from Different Social Groups in India: Prevalence, Determinants, and Transition Over Time (2005-2006 to 2019-2021).

Combating undernutrition among children under 5 years is presently an enormous challenge for India. The study aims to determine the prevalence of undernutrition by the Composite Index of Anthropometric Failure (CIAF) and the time-dependent significant determinants of undernutrition among children under 5 years from four recognized social groups, i.e., Scheduled Tribe (ST), Scheduled Caste (SC), Other Backward Class (OBC), and Others, or General group, between 2005-2006 and 2019-2021 in India. It also explains the transition in the probability of CIAF among ST, SC, OBC, and General children belonging to different socio-demographic, economic backgrounds, and geographic regions from 2005-2006 to 2015-2016, 2015-2016 to 2019-2021, and 2005-2006 to 2019-2021 in India. Time-dependent and time-independent logistic regression models are employed to identify the major determinants and predicted probabilities of CIAF, respectively, among four social groups. The predicted probabilities of CIAF among ST, SC, OBC, and General children belonging to various socio-demographic, economic backgrounds, and geographic regions are extracted from logistic regression models and represented graphically. The study outlines a higher prevalence of CIAF among ST children, followed by SC, OBC, and General children throughout the last 15 years. Since 2005-2006, the magnitude of CIAF risk elimination has been comparatively higher among socially marginalized children (ST, SC, OBC) than in General. The investigation also outlines a significant (p < 0.001), and consistent effect of child age, maternal nutritional level, education status, household economic status, and geographic regions on the prevalence of undernutrition among all four social groups in India from 2005-2006 to 2019-2021. The policymakers must focus much on the ST, SC, and OBC sections for eliminating childhood undernutrition. Specifically, more attention is needed for the ST, SC, and OBC children living with non- or less-educated mothers, belonging to poor families, living in central, western, and eastern Indian states for eliminating the childhood CIAF. This might contribute to lowering intergroup inequality (SDG 10.2) in India in terms of the incidence of hunger (SDG 2.2), undernutrition, and child mortality (SDG 3.2).

Drug delivery using biocompatible covalent organic frameworks (COFs) towards a therapeutic approach.

Covalent organic frameworks (COFs) are constructed exclusively with lightweight organic scaffolds, which can have a 2D or 3D architecture. The ease of synthesis, robust skeleton and tunable properties of COFs make them superior candidates among their counterparts for a wide range of uses including biomedical applications. In the biomedical field, drug delivery or photodynamic-photothermal (PDT-PTT) therapy can be individually considered a potential parameter to be investigated. Therefore, this comprehensive review is focused on drug delivery using COFs, highlighting the encapsulation and decapsulation of drugs by COF scaffolds and their delivery in biological media including live cells. Versatile COF scaffolds together with the delivery of several drug molecules are considered. We attempted to incorporate the status of drug encapsulation and decapsulation considering a wide range of recent publications.

Scourge of out-of-pocket expenditure on health: A study on its burden and predictors in a rural community of West Bengal.

Introduction: Globally, one-third of current health expenditure had been out-of-pocket expenditure (OOPE). The health system financing of almost all low- and middle-income countries including India rely heavily on out-of-pocket (OOP) payments for health care. OOPE on health payments is particularly hard on any community, especially the poor leading to incomplete or even no treatment during their ill health. This study estimated OOPE among residents of a rural community in West Bengal and explored the associated factors with high OOP expenses. Methods: A community-based cross-sectional study was conducted in a rural community in Singur, West Bengal from June 2019 to February 2020. The study was done among 398 villagers selected from 15 clusters or villages. Households were randomly selected in each village. All members of the selected households were interviewed. SPSS was used for data analysis both for descriptive and inferential statistics. Results: Only 14.6% of morbid persons had catastrophic expenditure. The incidence of catastrophic expenditure was higher among those who opted for private practitioners and or ayurveda, yoga and naturopathy, unani, siddha, and homeopathy (AYUSH) facilities. There was zero catastrophic expenditure for the unqualified sector. There was an increasing trend of OOP payments among the lower socioeconomic groups. Again, low-income individuals had a higher share in cumulative expenditure (Gini coefficient of 0.35). Most of the participants (78.4%) had no health insurance coverage. Conclusion: Promotion for higher utilization of public health facilities may reduce the burden of OOP expenses. Government health insurance schemes must be widened with the inclusion of coverage of outpatient services. Integrating AYUSH services in the public sector is another option to reduce OOP expenses.

The "LINC" between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis.

Previous research has shown that Δ40p53, the translational isoform of p53, can inhibit cell growth independently of p53 by regulating microRNAs. Here, we explored the role of Δ40p53 in regulating the long noncoding RNA-micro-RNA-cellular process axis, specifically focusing on LINC00176. Interestingly, LINC00176 levels were predominantly affected by the overexpression/stress-mediated induction and knockdown of Δ40p53 rather than p53 levels. Additional assays revealed that Δ40p53 transactivates LINC00176 transcriptionally and could also regulate its stability. RNA immunoprecipitation experiments revealed that LINC00176 sequesters several putative microRNA targets, which could further titrate several mRNA targets involved in different cellular processes. To understand the downstream effects of this regulation, we ectopically overexpressed and knocked down LINC00176 in HCT116 p53-/- (harboring only Δ40p53) cells, which affected their proliferation, cell viability, and expression of epithelial markers. Our results provide essential insights into the pivotal role of Δ40p53 in regulating the novel LINC00176 RNA-microRNA-mRNA axis independent of FL-p53 and in maintaining cellular homeostasis.

Dietary diversity and association with non-communicable diseases (NCDs) among adult men (15-54 years): A cross-sectional study using National Family and Health Survey, India.

A healthy and diversified diet is essential for preventing several non-communicable diseases (NCDs). Given the increasing evidence of diet-related health burdens and the rising prevalence of NCDs among Indian adults, the present study aims to explore dietary diversity patterns among adult men in India and their association with non-communicable diseases (NCDs). For this purpose, the study used the fourth round of the National Family and Health Survey (NFHS-4) to analyze adult male samples (n = 1,12,122). Dietary Diversity Scores (DDS) were computed by the weighted sum of the number of different food groups consumed by an individual. The prevalence of diabetes, heart disease, and cancer among adult men is considered a non-communicable disease. Bivariate and logistic regression was carried out to examine the association between DDS and NCDs by estimating chi-squared tests (χ2-test), odds ratio (OR), and 95% confidence interval (CI). The prevalence of diabetes, heart disease, and cancer among adult men in India is 2.1 percent, 1.2 percent, and 0.3 percent, respectively. Results show a positive association between dietary diversity score and the prevalence of the non-communicable disease. High-level dietary diversity scores increase to two times the likelihood of diabetes (OR 2.15 with p<0.05) among adult men than to better-off counterparts while controlling all the covariates. However, a moderate dietary diversity score significantly decreases the likelihood of heart disease (OR 0.88 with p<0.10) and Cancer (OR 0.71 with p<0.05) for adult men compared to a lower score of dietary diversity. In addition, age, marital status, drinking and smoking habits, occupation, and wealth index are also significantly associated with the odds of non-communicable diseases among adult men.

Structure-metal ion selectivity of rhodamine-based chemosensors.

Rhodamine-based chemosensors are widely used for the detection of various metal ions and applied in many fields of science including biological and environmental sciences. Rhodamine derivatives remain colorless and almost nonfluorescent when their spirolactam ring remains in closed form. They become pink or purple and strongly fluorescent upon opening of the ring. A particular metal ion can induce the ring opening process under a set of conditions and the process of selective sensing is dependent on many factors. Differentiation of metal sensing using rhodamine dyes is achieved in various ways which include selection of solvent, pH, mode of interaction with the cations, and so on. We have incorporated more than 140 research articles here to discuss the structure-property correlation of rhodamine based chemosensors. We have tried to correlate metal ion selectivity and structures of the chemosensors for the first time for rhodamine derivatives.

Determinants and transition of anaemia among under-five children from different social groups in India from 2005-06 to 2015-16.

Anaemia among under-five children is a global health problem and a major cause of child morbidity and mortality, especially in Lower-Middle-Income countries including India. Despite a significant decrease over the last decade, nearly 58% of children in India suffered from anaemia in 2015-16. This national average hides the inequality in the prevalence of anaemia among indigenous people and other social groups. Therefore, the study focuses on identifying time-dependent significant determinants of the prevalence of anaemia from 2005-06 to 2015-16 among children belonging to Scheduled Tribe (ST), Scheduled Caste (SC), Other Backward Class (OBC) and Other or General social groups. Besides, it also identified social group-wise transition of anaemia among under-five children belonging to different socio-demographic, economic, residential and regional backgrounds in India. Time-dependent and independent logistic regression models were used to identify significant determinants of child anaemia and the mean probability of anaemia across different categories of explanatory backgrounds. Though the probability of anaemia has decreased more among marginalized children during the last decade, it remains relatively higher among them. The study has outlined the significant effects of child age, birth order, maternal anaemia, education level and geographic regions on the prevalence of anaemia among ST, SC, OBC and General social groups in India over the past decade. The effect of economic status on the prevalence of anaemia among ST and SC children was insignificant. Four subpopulations demonstrated a relatively greater magnitude of decadal anaemia risk reduction among children of early age groups, living with teenage, non-anaemic, less educated mothers and living in northeast India. The study suggests the arrangement of region-specific, social-group based strategies for reducing the prevalence of anaemia among under-five children in India. In this way, the nation can achieve "health and well-being for all" (SDG 03) by eliminating the geographical, and social inequality in the prevalence of child anaemia within the country (SDG 10).

Amide bond hydrolysis of peptoids.

Incorporating a chiral non-coordinating substitution at the N-terminal end within peptoids facilitates regio-selective amide bond hydrolysis mediated by a transition metal ion and/or an acidic buffer as evident by X-ray crystallographic analysis, supported by ESI-MS. This opens up a new direction for peptidomimetic compounds towards future application in chemistry, biology and medicine.

A rhodamine based dual chemosensor for Al3+ and Hg2+: Application in the construction of advanced logic gates.

A rhodamine-based compound (RBO), which has been constructed from the reaction between N-(rhodamine-6G)lactam-ethylenediamine and 2,1,3-benzoxadiazole-4-carbaldehyde, is reported here as a selective chemosensor for both Al3+ and Hg2+ ions in 10 mM HEPES buffer in water:ethanol (1:9, pH = 7.4). Absorption intensity of RBO increases considerably at 528 nm with these cations. It shows fluorescence enhancement at 550 nm by 1140- and 524-fold in the presence of Al3+ and Hg2+, respectively. LOD has been determined as 6.54 and 16.0 nM for Al3+ and Hg2+, respectively. Quantum yield and lifetime of RBO enhances with these metal ions. Fluorescence intensity of Al-probe complex or Hg-probe complex is quenched in the presence of fluoride or sulfide ion, respectively, opening a path for the construction logic gates. DFT analysis has been used to understand the spectral transitions. We have constructed a systematic development from single to five inputs complex circuit, and for the first time a time dependent five input complex logic circuit is reported herein.

Determinants of time-trends in exclusivity and continuation of breastfeeding in India: An investigation from the National Family Health Survey.

Breastfeeding is an essential key factor for reducing child mortality and the risk of disease. Therefore, to ensure health and wellbeing for all (Sustainable Development Goal 03), and to reduce inequalities in child health status (SDG 10), understanding the determinants of breastfeeding is essential. Our research aims to investigate determinants of different breastfeeding practices from 2005-06 (NFHS-3) to 2015-16 (NFHS-4), and changes in different breastfeeding practices among various demographic, social, religious, and economic groups during this decade. We have used a multivariate binary logistic regression model to estimate significant determinants of different breastfeeding practices. The results show an 8.4% hike in Exclusive Breastfeeding (EBF), along with a 3.3% and 1% drop in the Continuation of Breastfeeding (CBF) up to one and two years respectively during this decade in India. Significant variation has been found in EBF, CBF1 and CBF2 among various categories of child's birth interval, place of residence, social groups, economic communities, and geographic regions. Maternal nutritional status and anemia levels had significant influence on CBF1 and CBF2, and gender of the children on EBF and CBF2 from 2005-06 to 2015-16. There was no significant variation in CBF1 and CBF2 among children born in different birth orders, whereas EBF was significantly less among higher birth orders children. A dramatic improvement in EBF was found among first birth ordered children, teenage and/or highly educated mother, rich families, and in north India, and CBF2 was significantly raised only among higher educated mothers. The estimation of determinants throughout the decade is essential for improving government policies related to supporting and encouraging breastfeeding. The study suggests more initiatives and investment for the promotion, support and improvement of CBF for one and two years, and reduction of inequality among various demographic and socio-economic groups and geographic regions.

Factors Associated with Intention and Attempt to Quit: A Study among Current Smokers in a Rural Community of West Bengal.

CONTEXT: Tobacco smoking is one of the preventable causes of death. Global Adult Tobacco Survey 2 report showed that 19% Indian males were current smokers. It is important to find out factors which help smokers on smoking cessation, ultimately to prevent of lung and other morbidities. There are few community-based studies on intention and attempt to quit smoking in rural area. AIMS: The present study aimed to determine the factors associated with intention and attempt to quit smoking among current smokers. SETTINGS AND DESIGN: A cross-sectional study was conducted from June to September 2019 among 198 male daily smokers residing in the rural field practice area of AllH and PH, Kolkata. SUBJECTS AND METHODS: After cluster sampling, data were collected by predesigned schedule by the face-to-face interview. RESULTS: 151 (76.3%) study subjects intended to quit smoking. 63 (31.8%) study subjects attempted to quit in last 1 year. Thirty-one (47.5%) showed high-to-medium nicotine dependence. There was a significant association of intention to quit with agriculture as occupation (acquisitive crime [AOR]-2.17, confidence interval [CI]-1.01-4.63), low nicotine dependence (AOR-2.98, CI-1.43-6.21), doctor's advice (AOR = 2.84, CI-1.27-6.33), and family pressure (AOR = 2.16, CI-1.07-4.38). Attempt to quit was significantly associated with low nicotine dependence (AOR = 5.85, CI-2.85-12.00), family pressure (AOR = 2.94, CI-1.47-5.91). CONCLUSION: Along with counseling to reduce nicotine dependence, comprehensive approach both from family members as well as health care providers, is vital to escalate the quitting behaviour in smoking habit.

A Di-Copper-Peptoid in a Noninnocent Borate Buffer as a Fast Electrocatalyst for Homogeneous Water Oxidation with Low Overpotential.

Water electrolysis is a promising approach toward low-cost renewable fuels; however, the high overpotential and slow kinetics limit its applicability. Studies suggest that either dinuclear copper (Cu) centers or the use of borate buffer can lead to efficient catalysis. We previously demonstrated the ability of peptoids-N-substituted glycine oligomers-to stabilize high-oxidation-state metal ions and to form self-assembled di-copper-peptoid complexes. Capitalizing on these features herein we report on a unique Cu-peptoid duplex, Cu2(BEE)2, that is a fast and stable homogeneous electrocatalyst for water oxidation in borate buffer at pH 9.35, with low overpotential and a high turnover frequency of 129 s-1 (peak current measurements) or 5503 s-1 (FOWA); both are the highest reported for Cu-based water electrocatalysts to date. BEE is a peptoid trimer having one 2,2'-bipyridine ligand and two ethanolic groups, easily synthesized on solid support. Cu2(BEE)2 was characterized by single-crystal X-ray diffraction and various spectroscopic and electrochemical techniques, demonstrating its ability to maintain stable in four cycles of controlled potential electrolysis, leading to a high overall turnover number of 51.4 in a total of 2 h. Interestingly, the catalytic activity of control complexes having only one ethanolic side chain is 2 orders of magnitude lower than that of Cu2(BEE)2. On the basis of this comparison and on mechanistic studies, we propose that the ethanolic side chains and the borate buffer have significant roles in the high stability and catalytic activity of Cu2(BEE)2; the -OH groups facilitate protons transfer, while the borate species enables oxygen transfer toward O-O bond formation.