Palmitoleate protects against Lipopolysaccharide-induced Inflammation and Inflammasome Activity.

Inflammation is part of natural immune defense mechanism against any form of infection or injury. However, prolonged inflammation could perturb cell homeostasis and contribute to the development of metabolic and inflammatory diseases including maternal obesity, diabetes, cardiovascular diseases, and metabolic dysfunction-associated steatotic liver diseases. Polyunsaturated fatty acids have been shown to mitigate inflammatory response by generating specialized pro-resolving lipid mediators which take part in resolution of inflammation. Here, we show that palmitoleate, an omega-7 monounsaturated fatty acid exerts anti-inflammatory properties in response to lipopolysaccharide (LPS)-mediated inflammation. Exposure of bone-marrow derived macrophages (BMDMs) to LPS or TNFα induces robust increase in the expression of pro-inflammatory cytokines and supplementation of palmitoleate inhibited LPS-mediated upregulation of pro-inflammatory cytokines. We also observed that palmitoleate was able to block LPS+ATP-induced inflammasome activation mediated cleavage of pro-caspase 1 and pro-interleukin (IL)-1ß. Further, treatment of palmitoleate protects against LPS-induced inflammation in human THP-1 derived macrophages and trophoblasts. Co-exposure of LPS and palmitate (saturated free fatty acid) induces inflammasome and cell death in BMDMs, however, treatment of palmitoleate blocked LPS and palmitate-induced cell death in BMDMs. Further, LPS and palmitate together results in the activation of mitogen activated protein kinases (MAPK) and pretreatment of palmitoleate inhibited the activation of MAPKs and nuclear translocation of nuclear factor kappa B (NF-kB) in BMDMs. In conclusion, palmitoleate shows anti-inflammatory properties against LPS-induced inflammation and LPS+palmitate/ATP-induced inflammasome activity and cell death.

A Covalent Triazine Framework for Photocatalytic Anti-Markovnikov Hydrofunctionalizations.

Porous materials-based heterogeneous photocatalysts, performing selective organic transformations, are increasing the applicability of photocatalytic reactions due to their ability to merge traditional photocatalysis with structured pores densely decorated with catalytic moiety for efficient mass and charge transfer, as well as added recyclability. We herein disclose a porous crystalline covalent triazine framework (CTF)-based heterogeneous photocatalyst that exhibits excellent photoredox properties for different hydrofunctionalization reactions such as hydrocarboxylations, hydroamination and hydroazidations. The high oxidizing property of this CTF enables the activation of styrenes, followed by regioselective C-N and C-O bond formation at ambient conditions. A change in the physicochemical and optoelectronic properties of the CTF, upon protonation during catalysis, lies at the basis of its photocatalytic properties. This allows us to obtain hydrocarboxylations, hydroamination, and hydroazidations from a myriad of electron-donating and -withdrawing aromatic and aliphatic substrates. This catalytic approach is further extended to late-stage functionalization of bio-active molecules. Finally, detailed characterizations of the CTF and further mechanistic investigations provides mechanistic insights in these reactions.

Effects of High-Intensity, Eccentric-Only Muscle Actions on Serum Biomarkers of Collagen Degradation and Synthesis.

ABSTRACT: Neltner, TJ, Sahoo, PK, Smith, RW, Anders, JPV, Arnett, JE, Ortega, DG, Schmidt, RJ, Johnson, GO, Natarajan, SK, and Housh, TJ. Effects of high-intensity, eccentric-only muscle actions on serum biomarkers of collagen degradation and synthesis. J Strength Cond Res 37(9): 1729-1737, 2023-The purpose of this study was to examine the effects of high-intensity, eccentric-only muscle actions of the leg extensors on (a) serum biomarkers of collagen degradation (hydroxyproline [HYP] and C-terminal telopeptide of type I collagen [C1M]) and synthesis (pro-c1α1) and (b) the time course of changes in maximal voluntary isometric contraction (MVIC) and ratings of muscle soreness after the eccentric-only exercise bout. Twenty-five recreationally active men (mean ± SD: age = 21.2 ± 2.0 years) completed 5 sets of 10 bilateral, eccentric-only dynamic constant external resistance muscle actions of the leg extensors at a load of 110% of their concentric leg extension 1 repetition maximum. Analysis of variances (p < 0.05) and a priori planned pairwise comparisons using Bonferroni corrected (p < 0.0167) paired t tests were used to examine mean changes in blood biomarkers from baseline to 48 hours postexercise as well as in MVIC and soreness ratings immediately, 24 hours, and 48 hours postexercise. There were increases in HYP (3.41 ± 2.37 to 12.37 ± 8.11 µg·ml-1; p < 0.001) and C1M (2.50 ± 1.05 to 5.64 ± 4.89 µg·L-1; p = 0.003) from preexercise to 48 hours postexercise, but no change in pro-c1α1. Maximal voluntary isometric contraction declined immediately after the exercise bout (450.44 ± 72.80 to 424.48 ± 66.67 N·m; p = 0.002) but recovered 24 hours later, whereas soreness was elevated immediately (6.56 ± 1.58; p < 0.001), 24 hours (3.52 ± 1.53; p < 0.001), and 48 hours (2.60 ± 1.32; p = 0.001) postexercise. The eccentric-only exercise bout induced increases in collagen degradation but had no effect on collagen synthesis. These findings provide information for clinicians to consider when prescribing exercise after an acute injury or surgery.

Expansion of the measles and rubella laboratory network, India.

Objective: To expand the measles and rubella laboratory network of India by integrating new laboratories. Methods: In collaboration with the World Health Organization (WHO), the Indian government developed a 10-step scheme to systematically expand the number of laboratories performing serological and molecular testing for measles and rubella. The Indian Council of Medical Research and WHO identified suitable laboratories based on their geographical location, willingness, preparedness, past performance and adherence to national quality control and quality assurance mechanisms. The 10-step scheme was initiated with training on measles and rubella diagnostic assays followed by testing of both measles and rubella serology and molecular unknown panels, cross-verification with reference laboratories and ended with WHO on-site accreditation. Findings: After extensive training, technical support, funding and monitoring, all six selected laboratories attained passing scores of 90.0% or more in serological and molecular proficiency testing of measles and rubella. Since 2018, the laboratories are a part of the measles and rubella network of India. Within 12 months of initiation of independent reporting, the six laboratories have tested 2287 serum samples and 701 throat or nasopharyngeal swabs or urine samples. Conclusion: The process led to strengthening and expansion of the network. This proficient laboratory network has helped India in scaling up serological and molecular testing of measles and rubella while ensuring high quality testing. The collaborative model developed by the Indian government with WHO can be implemented by other countries for expanding laboratory networks for surveillance of measles and rubella as well as other infectious diseases.

Seropositivity of Chlamydia trachomatis & Toxoplasma gondii among male partners of infertile couples in Odisha, India: A facility-based exploratory study.

Chlamydia trachomatis (CT) is the most common curable sexually transmitted non-viral infection, which can cause urethritis, prostatitis, orchitis and epididymitis among males. Toxoplasma gondii, a protozoan causes toxoplasmosis among humans. These infections may lead to decreased fertility. Hence, this study was aimed to estimate the seropositivity of CT and T. gondii infection among the male partners of infertile couples in Odisha, India. In this facility-based cross-sectional study, first void urine, seminal fluid and blood sample were collected from 153 males attending infertility clinics including 74 healthy controls. Urine and seminal fluid were tested through polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay was used to detect immunoglobulin (Ig) G, IgA and IgM anti-Chlamydia and IgM anti-Toxoplasma antibodies through serum. The prevalence of CT was 1.26 per cent (95% CI: 0.03-6.85) as estimated from semen samples using PCR. We detected anti-Chlamydia antibodies IgM-four per cent [95% confidence interval (CI): 0.83-11.24]; IgA-28.16 per cent (95% CI: 18.13-40.09) and IgG-12.5 per cent (95% CI: 5.87-22.4) among participants. Anti-Toxoplasma antibodies IgM were observed in 27.63 per cent (95% CI: 17.98-39.08) of participants. None of the control samples were found positive. Overall seropositivity of CT and Toxoplasma infections is comparable, which suggests that greater attention is required for screening these infections at clinics, especially among infertile couples.

Mapping the distribution and trends of co-circulating dengue virus serotypes in Odisha, India: A retrospective facility-based analysis.

Background Dengue, caused by mosquito bite, is an emerging disease of international concern. Evidence regarding the prevalent dengue serotypes is scarce, but essential for its management during the outbreaks. Hence, we mapped the distribution and trends of currently prevalent dengue virus (DENV) serotypes in Odisha. Methods We conducted a facility-based retrospective study from referral samples sent for the diagnosis/confirmation of dengue in 2018. The samples were serologically tested for enzyme-linked immunosorbent assay (ELISA) IgM antibody and NS1. Only NS1-positive samples were chosen for sero-typing. A pool of 8-10 NS1-positive samples were analysed for district-wise serotypes. Ribonucleic acid extraction and nested polymerase chain reaction (PCR) was done from NS1-positive samples. The PCR products were then subjected to gel electrophoresis. Results A total of 2892 samples were screened for dengue virus across various districts of Odisha where 763 samples were found to be NS1-positive. Thirteen of 18 districts covering all topographies of Odisha predominantly had DENV2 serotype. Only few districts such as Balangir, Kalahandi and Rayagada had mixed serotypes. Conclusion Although DENV2 is predominantly prevalent, mixed serotypes too exist in Odisha. Evidence based on variations of dengue serotypes across topographies, seasons, gender and age groups may support public health efforts in preventing the disease.

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis.

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.

Omega-3 Fatty Acid-Derived Resolvin D2 Regulates Human Placental Vascular Smooth Muscle and Extravillous Trophoblast Activities.

Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue.

Species-specific and cross-reactive antigen of filarial worm: Brugia malayi and Setaria digitata.

BACKGROUND & OBJECTIVES: Generally filarial antigens have been found to be cross-reactive in nature. Identification of genus and species-specific antigens has not been successful so far. Due to lack of human adult filarial parasite, researchers have been using other adult worms like Setaria digitata, a cattle parasite or Brugia malayi, a rodent model for their research work. In this situation, specificity of the prepared antigen (S. digitata or B. malayi) to detect the antibodies to Wuchereria bancrofti is questionable. METHODS: In the present investigation, we have tested a panel of human sera (collected from the areas, endemic for bancroftian filariasis) to correlate the immune reactivity against somatic antigens of adult stages and microfilarial stages of S. digitata and B. malayi. Further, using intact microfilariae (mf) from the above two parasites along with W. bancrofti, we have analyzed the antibody response to the sheath antigens. A panel of infected human and cattle sera was tested by immunoperoxidase assay using intact mf of three different parasites, viz. W. bancrofti, B. malayi, and S. digitata. RESULTS: A very significant positive correlation in filarial Igs (polyvalent), IgG, IgM, IgE and IgG4 levels were found between the two adult somatic antigens of B. malayi and S. digitata when tested against human filarial sera. However, such a correlation was not found when mf antigens of B. malayi and S. digitata were tested against a panel of W. bancrofti sera indicating that antigens present in mf could be far less cross-reactive in comparison to those in adult stage parasites. INTERPRETATION & CONCLUSION: The results indicated the differential cross-reactivity of antisheath antibodies to the mf sheath of three different filarial parasites. Soluble antigens of S. digitata could inhibit antisheath antibody reactivity to only S. digitata mf sheath and not to mf sheath of W. bancrofti further confirming the specificity of sheath antigen.

Factors influencing implementation of mass drug administration for lymphatic filariasis elimination: a mixed-method study in Odisha, India.

Background: Lymphatic filariasis (LF) persists as a public health problem in India. Despite more than ten rounds of mass drug administration (MDA), LF continues to be endemic in the Dhenkanal district of Odisha. Hence, we assessed the coverage and compliance of the MDA program and explored the factors affecting it in the Dhenkanal district. Methods: An explanatory mixed-method study was conducted, wherein for the quantitative survey, 552 participants aged 2 years and above were recruited following a multistage cluster random sampling during February 2022. In-depth interviews were conducted among purposively selected key stakeholders and program implementers. Descriptive statistics were used to report coverage and compliance, along with a 95% confidence interval. Qualitative data were analyzed using a thematic approach. Results: We observed coverage of 99.28% and compliance of 85.87% for MDA drugs. Supervised drug administration proved to be a major pillar in increasing compliance. There was difficulty in administering drugs in urban areas due to gated societies, the absence of individuals during the day, and the perspective toward healthcare providers. Participants reported a lack of confidence in drug distributors and a fear of side effects as major causes for non-compliance. Conclusion: There is a need to strengthen MDA, especially in urban areas. An urban-specific strategy, along with surveillance, behavioral change communication, and the involvement of multi-disciplinary teams, is required.

Motivation-opportunity-ability-behaviour of community members and program implementers towards mass drug administration for lymphatic filariasis elimination in India: a systematic review and implementation priority.

Lymphatic filariasis (LF) is a significant public health issue in India. Despite 10-15 rounds of mass drug administration (MDA) in India, the global LF elimination target of 2030 appears challenging. To strengthen the program, community and provider perspectives on ways to bridge a gap in MDA are needed. Through the motivation-opportunity-ability-behaviour (MOAB) lens, we systematically reviewed the facilitators and barriers encountered in LF elimination in India. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched PubMed, Embase, ProQuest and Google Scholar databases to explore factors related to MDA program implementation in India through 30 June 2021. We analysed the data using a thematic framework. We identified 576 studies; of these, 20 studies were included. This review revealed that the public health system for distributing MDA drugs in India created a better enabling environment, including zero out-of-pocket expenditure, door-step distribution of medicines and ample capacity-building training and follow-up. However, community members were unaware of the rationale for drug consumption, leading to a gap in drug distribution and consumption. Motivation is required among community members, which suggests capacity-building training for service providers to counsel the community.

Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.

Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD), has emerged as the leading cause of liver failure and related death. Currently, no medication is specifically approved to treat NAFLD or NASH. Here we report that oral administration of honey vesicle-like nanoparticles (H-VLNs) to naturally aged mice protects the liver from NASH development. H-VLNs are dominantly taken up by Kupffer cells in the liver and suppress hepatic chronic inflammation and further development of fibrosis and nodule formation in aged mice. Besides their reported anti-inflammasome function, H-VLNs are found to inhibit the transcriptional activities of C-JUN and nuclear factor-kappa B (NF-κB). MicroRNAs miR5119 and miR5108 and phenolic compound luteolin in H-VLNs are identified in suppressing both the C-JUN and NF-κB pathways. Collectively, oral intake of H-VLNs represents a promising new user-friendly modality to prevent the development of NASH.

Unrevealing the role of metal oxide nanoparticles on biohydrogen production by Lactobacillus delbrueckii.

The positive interaction between Clostridium sp. and lactic acid-producing bacteria (Lactobacillus sp) is commonly seen in various high-rate hydrogen production systems. However, the exact role of the hydrogen production ability of Lactobacillus sp in a dark fermentation production system is rarely studied. Lactobacillus delbrueckii was herein used for the first time, to the best of the author's knowledge, to demonstrate biohydrogen production under anaerobic conditions. At first, the pH condition was optimized, followed by the addition of nanoparticles for enhanced biohydrogen production. Under optimized conditions of pH 6.5, substrate concentration 10 g/L, and 100 mg/L of NiO/Fe2O3, the maximum hydrogen yield (HY) of 1.94 mol/mol hexose was obtained, which is 18 % more than the control. The enhanced H2 production upon the addition of nanoparticles is supported via the external electron transfer (EET) mechanism, which regulates the metabolic pathway regulation with increased production of acetate and butyrate and reduced formation of lactate.

Effect of nano-metal doped calcium peroxide on biomass pretreatment and green hydrogen production from rice straw.

In this study, calcium peroxide was modified and doped with metal-based nanoparticles (NP) to enhance the efficiency of pretreatment and biohydrogen generation from RS. The findings revealed that the addition of MnO2-CaO2 NPs (at a dosage of 0.02 g/g TS of RS) had a synergistic effect on the breakdown of biomass and the production of biohydrogen. This enhancement resulted in a maximum hydrogen yield (HY) of 58 mL/g TS, accompanied by increased concentrations of acetic acid (2117 mg/L) and butyric acid (1325 mg/L). In contrast, RS that underwent pretreatment without the use of chemicals or NP exhibited a lower HY of 28 mL/g TS, along with the lowest concentrations of acetic acid (1062 mg/L) and butyric acid (697 mg/L). The outcome showed that supplementation of NP stimulated the pretreatment of RS and improved the formation of acetic and butyric acid through the regulation of metabolic pathways during acidogenic fermentation.

Human lymphatic filariasis: genetic polymorphism of endothelin-1 and tumor necrosis factor receptor II correlates with development of chronic disease.

BACKGROUND: Hydrocele and elephantiasis are 2 clinically very diverse and often mutually exclusive chronic manifestations of human bancroftian filariasis. Plasma levels of endothelin-1 (ET-1), a major angiogenic factor, and tumor necrosis factor receptors (TNFRs) that regulate host inflammation have been associated with development of chronic filariasis, although their genetic basis are not known. METHODS: We studied polymorphisms of ET-1 (Ala288Ser) and TNFR-II (Met196Arg) genes by means of the polymerase chain reaction confronting 2 pairs primers method and restriction fragment length polymorphism, respectively. Plasma ET-1 level was measured by enzyme-linked immunosorbent assay. RESULTS: Met196Arg genotype frequency of TNFR-II polymorphism was significantly greater in hydrocele patients, compared with elephantiasis patients (OR, 4.34 [95% CI, 2.04-9.20]). Conversely, a significantly high prevalence of the Ala288Ser mutation of ET-1 was observed in elephantiasis patients, compared with hydrocele cases (OR, 2.15 [95% CI, 1.13-4.10]). Decreased plasma ET-1 levels associated significantly with Ala288Ser mutation in the study population. A combined analysis indicated a 23-fold higher risk for developing elephantiasis in individuals with TNFR-II (Met196Met) and ET-1 mutants (Ala288Ser + Ser288Ser). CONCLUSIONS: ET-1 (Ala288Ser) and TNFR-II (Met196Arg) polymorphisms are associated with development of one or the other form of chronic disease in bancroftian filariasis.

Facilitators and barriers in implementation of mass drug administration for lymphatic filariasis elimination in India: A protocol for systematic review and qualitative meta-synthesis.

Introduction: Lymphatic filariasis (LF) is a debilitating and disabling parasitic disease of immense public health concern in India with more than 650 million people at risk. Mass drug administration (MDA) is the recommended preventive chemotherapy strategy to eliminate LF. But, its coverage and compliance has been a mixed success. There is an urgent need of evidence to strengthen the program further, which can be done by exploring and understanding implementer as well as beneficiary perspectives. Objective: To systematically review the facilitators and barriers experienced during the coverage and compliance of MDA for LF elimination in India from both beneficiary and provider's (health system) perspective. Methods and Analysis: We will search at Medline database through PubMed and Embase, along with ProQuest and Google Scholar to retrieve literature. Original qualitative observational studies exploring challenges and enablers in MDA program will be screened by two independent reviewers systematically based on title and abstract followed by full text. The risk of bias will be assessed through critical appraisal skills program checklist for each included article. Data will be extracted in a pre-designed proforma with study characteristics, demographic features, and texts and quotes of qualitative data. Data will be analyzed through thematic analysis and motivation-opportunity-ability-behavior framework using MAXQDA software. Ethics and Dissemination: This is a literature-based review with minimal privacy concerns. The findings of this study will be published in a peer-reviewed journal and disseminated through policy brief to program implementers.

Mass drug administration for lymphatic filariasis elimination amidst COVID-19 pandemic in Odisha, India: A step towards achieving SDG-3.

Sustainable Development Goal-3 (SDG) aims to eliminate lymphatic filariasis by 2030 through >65% coverage and compliance of mass drug administration (MDA), the preventive chemotherapy strategy of delivering anthelminthic drugs. However, the ongoing COVID-19 pandemic has disrupted such programmes, yet MDA was administered during February 2021 in Odisha, India. We aimed to assess the coverage and compliance of the present round of MDA amidst the pandemic and explore factors for non-compliance in Cuttack district of Odisha, a filariasis endemic area. Community-based participants enrolled through multistage stratified sampling were administered a semi-structured questionnaire following COVID-19 protocols. The coverage of MDA was 93.2% whereas consumption was 73.7%. Participants reported that healthcare workers were motivated and satisfactorily explained the benefits of MDA but still fear of side-effects was the major cause of non-compliance. Nonetheless, this recent round of MDA was effective, despite challenges posed by the ongoing pandemic.

Transition metal-free approach for late-stage benzylic C(sp3)-H etherifications and esterifications.

We report a transition metal-free approach for the regioselective functionalization of benzylic C(sp3)-H bonds using alcohols and carboxylic acids as the nucleophiles. This straightforward and general route has provided various benzylic ethers and esters, including twelve pharmaceutically relevant compounds.