High arsenic contamination in the breast milk of mothers inhabiting the Gangetic plains of Bihar: a major health risk to infants.

Groundwater arsenic poisoning has posed serious health hazards in the exposed population. The objective of the study is to evaluate the arsenic ingestion from breastmilk among pediatric population in Bihar. In the present study, the total women selected were n = 513. Out of which n = 378 women after consent provided their breastmilk for the study, n = 58 subjects were non-lactating but had some type of disease in them and n = 77 subjects denied for the breastmilk sample. Hence, they were selected for the women health study. In addition, urine samples from n = 184 infants' urine were collected for human arsenic exposure study. The study reveals that the arsenic content in the exposed women (in 55%) was significantly high in the breast milk against the WHO permissible limit 0.64 µg/L followed by their urine and blood samples as biological marker. Moreover, the child's urine also had arsenic content greater than the permissible limit (< 50 µg/L) in 67% of the studied children from the arsenic exposed regions. Concerningly, the rate at which arsenic is eliminated from an infant's body via urine in real time was only 50%. This arsenic exposure to young infants has caused potential risks and future health implications. Moreover, the arsenic content was also very high in the analyzed staple food samples such as rice, wheat and potato which is the major cause for arsenic contamination in breastmilk. The study advocates for prompt action to address the issue and implement stringent legislative measures in order to mitigate and eradicate this pressing problem that has implications for future generations.

Novel hybrids of 1,2,3-triazole-benzoxazole: design, synthesis, and assessment of DprE1 enzyme inhibitors using fluorometric assay and computational analysis.

Decaprenylphosphoryl-ß-D-ribose-oxidase (DprE1), a subunit of the essential decaprenylphosphoribose-2'-epimerase, plays a crucial role in the synthesis of cell wall arabinan components in mycobacteria, including the pathogen responsible for tuberculosis, Mycobacterium tuberculosis. In this study, we designed, synthesised, and evaluated 15 (BOK-1-BOK-10 and BOP-1-BOP-5) potential inhibitors of DprE1 from a series of 1,2,3-triazole ligands using a validated DprE1 inhibition assay. Two compounds, BOK-2 and BOK-3, demonstrated significant inhibition with IC50 values of 2.2 ± 0.1 and 3.0 ± 0.6 µM, respectively, whereas the standard drug (TCA-1) showed inhibition at 3.0 ± 0.2 µM. Through molecular modelling and dynamic simulations, we explored the structural relationships between selected 1,2,3-triazole compounds and DprE1, revealing key features for effective drug-target interactions. This study introduces a novel approach for designing ligands against DprE1, offering a potential therapeutic strategy for tuberculosis treatment.

Identification of 15 (BOK-1­BOK-10 and BOP-1­BOP-5) potent inhibitors of DprE1 enzyme from 1,2,3-triazole ligands.BOK-2 and BOK-3 exhibited significant DprE1 inhibition with IC₅₀ values of 2.2 ± 0.1 and 3.0 ± 0.6 µM, respectively.Molecular modelling and dynamic simulations elucidated key structural features for effective drug­target interactions.Novel approach introduced for designing DprE1 ligands, potentially aiding tuberculosis treatment.Findings offer promising candidates for future tuberculosis research.

Advances in HER2-Targeted Therapies: From monoclonal antibodies to dual inhibitors developments in cancer treatment.

HER2 receptors, overexpressed in certain human cancers, have drawn significant attention in cancer research due to their correlation with poor survival rates. Researchers have developed monoclonal antibodies like Trastuzumab and Pertuzumab against HER2 receptors, which have proven highly beneficial in cancer therapy. Bispecific antibodies like Zanidatamab and antibody-drug conjugates like T-DM1 have been developed to overcome the resistance associated with monotherapy. Small molecules such as Lapatinib, Neratinib, and Pyrotinib were initially developed for treating breast cancer. However, ongoing research is investigating their potential use in other types of cancer, often in combination with other medications. EGFR/HER2 dual-targeted drugs have overcome drug resistance associated with HER2-targeted monotherapy. This comprehensive review covers the structural characteristics of HER2, the HER family signaling pathway mechanism, recent findings regarding HER2 receptor involvement in various cancers, and diverse HER2-targeted therapies. This information provides a comprehensive understanding of HER2-targeted strategies in the evolving field of cancer treatment.

High lead contamination in Mother's breastmilk in Bihar (India): Health risk assessment of the feeding children.

Lead poisoning in the recent times has caused serious health threats in the exposed human population. It is estimated that about 815 million people are exposed to lead poisoning worldwide and in India total 275 million children are exposed to blood lead contamination. The present study was carried outed in 6 districts of Bihar to know the extent of lead exposure in the children through their mother's breastmilk. The biological samples such as breastmilk, mother's urine, child's urine, and mother's blood samples were collected for quantitative lead estimation. Moreover, the selected household water sources (handpump) and the food consumed by the individuals-wheat, rice and potato samples were also collected for lead quantification. The study reveals that the breastmilk had high lead content in 92% of the samples (highest value 1309 µg/L), in blood presence of lead was observed in 87% studied samples (highest value 677.2 µg/L). In mother's urine the highest lead value was 4168 µg/L (62%) and in child's urine the highest value was 875.4 µg/L (62%) respectively of the studied samples. Moreover, in the studied food samples, wheat had lead content in 45% the studied samples (highest value 7910 µg/kg). In rice in 40% of the studied samples (highest value 6972 µg/kg) and in potato 90% of the studied samples (highest value = 13786 µg/kg) were found with elevated lead content respectively. The hazard quotient (HQ) and the cancer risk (CR) for lead contamination was very much higher in mothers followed by their children. The entire study indicated that lead exposure through food (wheat, rice and potato) has reached the mother's breastmilk and from their it has reached their child's body. This could cause serious hazards in the exposed children causing serious neurological damages, low IQ, low memory, and low mental growth in them. Therefore, a strategic action is required to control the present problem.

Disposable electrochemical sensors based on reduced graphene oxide/polyaniline/poly(alizarin red S)-modified integrated carbon electrodes for the detection of ciprofloxacin in milk.

An electrochemical sensor based on an electroactive nanocomposite was designed for the first time consisting of electrochemically reduced graphene oxide (ERGO), polyaniline (PANI), and poly(alizarin red S) (PARS) for ciprofloxacin (CIPF) detection. The ERGO/PANI/PARS-modified screen-printed carbon electrode (SPCE) was constructed through a three-step electrochemical protocol and characterized using FTIR, UV-visible spectroscopy, FESEM, CV, LSV, and EIS. The new electrochemical CIPF sensor demonstrated a low detection limit of 0.0021 µM, a broad linear range of 0.01 to 69.8 µM, a high sensitivity of 5.09 µA/µM/cm2, and reasonable selectivity and reproducibility. Moreover, the ERGO/PANI/PARS/SPCE was successfully utilized to determine CIPF in milk with good recoveries and relative standard deviation (< 5%), which were close to those with HPLC analysis.

Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices.

Nanoparticulate drug delivery systems (NDDS) based nanoformulations have emerged as promising drug delivery systems. Various NDDS-based formulations have been reported such as polymeric nanoparticles (NPs), nanoliposomes, solid lipid NPs, nanocapsules, liposomes, self-nano emulsifying drug delivery systems, pro liposomes, nanospheres, microemulsion, nanoemulsion, gold NPs, silver NPs and nanostructured lipid carrier. They have shown numerous advantages such as enhanced bioavailability, aqueous solubility, permeability, controlled release profile, and blood-brain barrier (BBB) permeability. This advantage of NDDS can help to deliver pure drugs to the target site. However, the formulation of nanoparticles is a complex process that requires optimization to ensure product quality and efficacy. Quality by Design (QbD) is a systemic approach that has been implemented in the pharmaceutical industry to improve the quality and reliability of drug products. QbD involves the optimization of different parameters like zeta potential (ZP), particle size (PS), entrapment efficiency (EE), polydispersity index (PDI), and drug release using statistical experimental design. The present article discussed the detailed role of QbD in optimizing nanoformulations and their advantages, advancement, and applications from the industrial perspective. Various case studies of QbD in the optimization of nanoformulations are also discussed.

Analysis of the gamma index using an indigenously developed anthropomorphic heterogeneous female pelvis (AHFP) phantom.

BACKGROUND: It is essential in modern radiotherapy treatment practices to evaluate the quality assurance (QA) of the treatment plan prior to the exclusion of patient from treatment. The typical suitable tools used for patient pretreatment QA are phantoms representing the human anatomy. An anthropomorphic heterogeneous female pelvic (AHFP) phantom has been developed to represent the real female pelvic structure. PURPOSE: The objective of the current study is to assess the findings of relative dosimetry carried out utilizing an electronic portal imaging device (EPID) on the AHFP phantom fabricated. METHODS: The planning target volume (PTV) was created on CT slices of an AHFP phantom to confirm the tool's ability to represent female pelvic anatomy and serve as a QA tool. In order to assess the dose received by healthy organs during radiotherapy, organs at risk such as the bladder and rectum were additionally drawn alongside the PTV. Rapid Arc and Intensity modulated radiation therapy (IMRT) were both used to create the treatment plan on treatment planning system, and the Anisotropic Analytical Algorithm Version 11.0.31 was used to calculate the dose. RESULTS: The results obtained for the average gamma value in RapidArc plans are 0.26, 0.27, and 0.28 (g ≤1) and IMRT plans are 0.39, 0.40, and 0.46 (g ≤1) for target 1, target 2, and target 3, respectively. CONCLUSION: According to the findings of the current study, the AHFP phantom was used to explore the potential of relative dosimetry using EPID as a QA tool, which was found to be suitable.

Hemodynamic evaluation of biomaterial-based surgery for Tetralogy of Fallot using a biorobotic heart, in silico, and ovine models.

Tetralogy of Fallot is a congenital heart disease affecting newborns and involves stenosis of the right ventricular outflow tract (RVOT). Surgical correction often widens the RVOT with a transannular enlargement patch, but this causes issues including pulmonary valve insufficiency and progressive right ventricle failure. A monocusp valve can prevent pulmonary regurgitation; however, valve failure resulting from factors including leaflet design, morphology, and immune response can occur, ultimately resulting in pulmonary insufficiency. A multimodal platform to quantitatively evaluate the effect of shape, size, and material on clinical outcomes could optimize monocusp design. This study introduces a benchtop soft biorobotic heart model, a computational fluid model of the RVOT, and a monocusp valve made from an entirely biological cell-assembled extracellular matrix (CAM) to tackle the multifaceted issue of monocusp failure. The hydrodynamic and mechanical performance of RVOT repair strategies was assessed in biorobotic and computational platforms. The monocusp valve design was validated in vivo in ovine models through echocardiography, cardiac magnetic resonance, and catheterization. These models supported assessment of surgical feasibility, handling, suturability, and hemodynamic and mechanical monocusp capabilities. The CAM-based monocusp offered a competent pulmonary valve with regurgitation of 4.6 ± 0.9% and a transvalvular pressure gradient of 4.3 ± 1.4 millimeters of mercury after 7 days of implantation in sheep. The biorobotic heart model, in silico analysis, and in vivo RVOT modeling allowed iteration in monocusp design not now feasible in a clinical environment and will support future surgical testing of biomaterials for complex congenital heart malformations.

HPV DNA status and clinical history of patients are supplements for accurate reporting of the cytological Pap smear.

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test.

Bioflavonoid combination attenuates diabetes-induced nephropathy in rats via modulation of MMP-9/TIMP-1, TGF-ß, and GLUT-4-associated pathways.

Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.

Psychological health among healthcare professionals during COVID-19 pandemic: An updated meta-analysis.

Background: The coronavirus disease 2019 (COVID-19) pandemic outbreak created a challenge to manage the health, especially the mental health of various care providers involved in treating the patients infected with the virus. Previously published literature has shown a significant effect of the pandemic on the psychological health of healthcare workers (HCWs) globally; so, this study aimed to describe the psychological health outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Indian HCWs. Methods: An extensive literature search was conducted in databases including PubMed and Google Scholar. The search was restricted from the COVID-19 outbreak until June 2022. Cross-sectional studies and other studies (telephonic interviews and survey-based studies) reported the prevalence of anxiety and depression among frontline HCWs since the onset of the COVID-19 pandemic. All the studies were critically evaluated by two individual authors in terms of screening and methodological quality evaluation. A total of 16 studies were included in the final meta-analysis. Results: The prevalence of depression among n = 12231 participants of 14 studies was 0.37 CI 95% [0.28-0.48]; the prevalence of anxiety among n = 9467 participants of 12 studies was 0.39 CI 95% [0.29-0.49]. The results of the overall meta-analysis indicate that 37% and 39% of HCWs in this study experienced mild-to-severe depression and anxiety, respectively. During the COVID-19 pandemic, a significant number of HCWs developed mental health issues, with a reported prevalence of depression (37%) and anxiety (39%). Conclusion: Frontline HCWs' mental health should get full consideration during public health emergencies, screening should be actively conducted, and specific steps should be taken to lower the fear associated with the risk of infections.

Computational and biological approaches in repurposing ribavirin for lung cancer treatment: Unveiling antitumorigenic strategies.

Lung cancer is among leading causes of death worldwide. The five-year survival rate of this disease is extremely low (17.8 %), mainly due to difficult early diagnosis and to the limited efficacy of currently available chemotherapeutics. This underlines the necessity to develop innovative therapies for lung cancer. In this context, drug repurposing represents a viable approach, as it reduces the turnaround time of drug development removing costs associated to safety testing of new molecular entities. Ribavirin, an antiviral molecule used to treat hepatitis C virus infections, is particularly promising as repurposed drug for cancer treatment, having shown therapeutic activity against glioblastoma, acute myeloid leukemia, and nasopharyngeal carcinoma. In the present study, we thoroughly investigated the in vitro anticancer activity of ribavirin against A549 human lung adenocarcinoma cells. From a functional standpoint, ribavirin significantly inhibits cancer hallmarks such as cell proliferation, migration, and colony formation. Mechanistically, ribavirin downregulates the expression of numerous proteins and genes regulating cell migration, proliferation, apoptosis, and cancer angiogenesis. The anticancer potential of ribavirin was further investigated in silico through gene ontology pathway enrichment and protein-protein interaction networks, identifying five putative molecular interactors of ribavirin (Erb-B2 Receptor Tyrosine Kinase 4 (Erb-B4); KRAS; Intercellular Adhesion Molecule 1 (ICAM-1); amphiregulin (AREG); and neuregulin-1 (NRG1)). These interactions were characterized via molecular docking and molecular dynamic simulations. The results of this study highlight the potential of ribavirin as a repurposed chemotherapy against lung cancer, warranting further studies to ascertain the in vivo anticancer activity of this molecule.

Revolutionizing biomedicine: Aptamer-based nanomaterials and nanodevices for therapeutic applications.

With the progress in two distinct areas of nanotechnology and aptamer identification technologies, the two fields have merged to what is known as aptamer nanotechnology. Aptamers have varying properties in the biomedical field include their small size, non-toxicity, ease of manufacturing, negligible immunogenicity, ability to identify a wide range of targets, and high immobilizing capacity. Nevertheless, aptamers can utilize the distinct characteristics offered by nanomaterials like optical, magnetic, thermal, electronic properties to become more versatile and function as a novel device in diagnostics and therapeutics. This engineered aptamer conjugated nanomaterials, in turn provides a potentially new and unique properties apart from the pre-existing characteristics of aptamer and nanomaterials, where they act to offer wide array of applications in the biomedical field ranging from drug targeting, delivery of drugs, biosensing, bioimaging. This review gives comprehensive insight of the different aptamer conjugated nanomaterials and their utilization in biomedical field. Firstly, it introduces on the aptamer selection methods and roles of nanomaterials offered. Further, different conjugation strategies are explored in addition, the class of aptamer conjugated nanodevices being discussed. Typical biomedical examples and studies specifically, related to drug delivery, biosensing, bioimaging have been presented.

A Comprehensive Review and Androgen Deprivation Therapy and Its Impact on Alzheimer's Disease Risk in Older Men with Prostate Cancer.

Prostate cancer (PCa) is one of the most prevalent malignancies affecting males worldwide. Despite reductions in mortality rates due to advances in early identification and treatment methods, PCa remains a major health concern. Recent research has shed light on a possible link between PCa and Alzheimer's disease (AD), which is a significant neurological ailment that affects older males all over the world. Androgen deprivation therapy (ADT), a cornerstone therapeutic method used in conjunction with radiation and palliative care in advanced metastatic PCa cases, is critical for disease management. Evidence reveals a relationship between ADT and cognitive impairment. Hormonal manipulation may cause long-term cognitive problems through processes such as amyloid beta (Aß) aggregation and neurofibrillary tangles (NFTs). Fluctuations in basal androgen levels can upset the delicate balance of genes that are sensitive to androgen levels, contributing to cognitive impairment. This detailed review dives into the various aspects of PCa aetiology and its relationship with cognitive decline. It investigates the discovery of particular biomarkers, as well as microRNAs (miRNAs), which play important roles in pathogenic progression. The review attempts to identify potential biomarkers associated with ADT-induced cerebral changes, including Aß oligomer buildup, NFT formation, and tauopathy, which can contribute to early-onset dementia and cognitive impairment. Besides it further aims to provide insights into innovative diagnostic and therapeutic avenues for alleviating PCa and ADT-related cognitive sequelae by unravelling these complicated pathways and molecular mechanisms.

Advancements in combining targeted therapy and immunotherapy for colorectal cancer.

Colorectal cancer (CRC) is a prevalent gastrointestinal cancer posing significant clinical challenges. CRC management traditionally involves surgery, often coupled with chemotherapy. However, unresectable or metastatic CRC (mCRC) presents a complex challenge necessitating innovative treatment strategies. Targeted therapies have emerged as the cornerstone of treatment in such cases, with interventions tailored to specific molecular attributes. Concurrently, immunotherapies have revolutionized cancer treatment by harnessing the immune system to combat malignant cells. This review explores the evolving landscape of CRC treatment, focusing on the synergy between immunotherapies and targeted therapies, thereby offering new avenues for enhancing the effectiveness of therapy for CRC.

Curcumin-loaded liposomes modulating the synergistic role of EpCAM and estrogen receptor alpha in lung cancer management.

Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, necessitating the exploration of innovative therapeutic strategies. This study delves into the in vitro potential of liposomal therapeutics utilizing Curcumin-loaded PlexoZome® (CUR-PLXZ) in targeting EpCAM/TROP1 and Estrogen Receptor Alpha (ERα) signalling pathways for LC management. The prevalence of LC, particularly non-small cell lung cancer (NSCLC), underscores the urgent need for effective treatments. Biomarkers like EpCAM/TROP1 and ERα/NR3A1 play crucial roles in guiding targeted therapies and influencing prognosis. EpCAM plays a key role in cell-cell adhesion and signalling along with ERα which is a nuclear receptor that binds estrogen and regulates gene expression in response to hormonal signals. In LC, both often get overexpressed and are associated with tumour progression, metastasis, and poor prognosis. Curcumin, a phytochemical with diverse therapeutic properties, holds promise in targeting these pathways. However, its limited solubility and bioavailability necessitate advanced formulations like CUR-PLXZ. Our study investigates the biological significance of these biomarkers in the A549 cell line and explores the therapeutic potential of CUR-PLXZ, which modulates the expression of these two markers. An in vitro analysis of the A549 human lung adenocarcinoma cell line identified that CUR-PLXZ at a dose of 5 µM effectively inhibited the expression of EpCAM and ERα. This finding paves the way for targeted intervention strategies in LC management.

Design, synthesis and evaluation of new thiazolidin-4-ones as LPA1 receptor antagonists for breast cancer therapy.

Aim: Breast cancer has been a leading cause of mortality among women worldwide in recent years. Targeting the lysophosphatidic acid (LPA)-LPA1 pathway using small molecules could improve breast cancer therapy. Materials & methods: Thiazolidin-4-ones were developed and tested on MCF-7 cancer cells, and active compounds were analyzed for their effects on apoptosis, migration angiogenesis and LPA1 protein and gene expression. Results & conclusion: Compounds TZ-4 and TZ-6 effectively reduced the migration of MCF-7 cells, and induced apoptosis. TZ-4, TZ-6, TZ-8 and TZ-14 significantly reduced the LPA1 protein, LPA1 and angiogenesis gene expression in treated MCF-7 cells. Molecular docking and molecular dynamic simulation studies reveal the ligand interactions and stability of the LPA1-ligand complex. Developed thiazolidin-4-ones showed great potential as an LPA1-targeted approach to combating breast cancer.

Breast cancer is a major cause of death for women worldwide. Using small molecules to target the lysophosphatidic acid (LPA)­LPA₁ pathway could improve breast cancer treatment. We tested a type of molecule called thiazolidin-4-ones on breast cancer cells in the lab. We looked at how these molecules affected cell death, movement, blood vessel growth and the activity of the LPA₁ gene and protein. Some of these molecules, such as TZ-4 and TZ-6, reduced the movement of cancer cells and caused them to die. They also decreased the levels of LPA₁ protein and gene activity in the cells. We used computer simulations to see how these molecules interacted with the LPA₁ protein. Our findings suggest that thiazolidin-4-ones could be a promising treatment for breast cancer by targeting LPA₁.

Lignin phenolation by graft copolymerization to boost its reactivity.

Lignin is the most abundant phenolic biopolymer and a renewable resource of aromatics. It can be used as a phenol substitute in the synthesis of phenolic resins. However, lignin is not as reactive as phenol, so phenolation is generally carried out to improve lignin reactivity. In this work, we suggest a solution to circumvent the limitations of traditional phenolation (e.g., high temperature, strong acids/bases, limited reactivity, and phenol toxicity). We first attempt new lignin phenolation by graft copolymerization in which polymeric phenol, instead of toxic phenol, is introduced to lignin. Organosolv lignin from hardwood was modified with 2-bromoisobutyryl bromide to act as a lignin macroinitiator (L-Br). A protected phenolic monomer, 4-acetoxystyrene, was graft copolymerized onto L-Br using CuBr2/tris[2-(dimethylamino)ethyl]amine as a catalyst/ligand, after which the resultant lignin copolymer was deacetylated to produce lignin grafted with poly(4-hydroxystyrene). This poly-phenolation process was conducted at room temperature without the strong acids/bases and toxic phenol required in conventional phenolation. The poly-phenolated lignin was analyzed using 1H-, 13C-, and 31P NMR spectroscopy and gel permeation chromatography. This novel phenolation process enhanced the reactive sites of lignin more than tenfold. It also reduced the dark color of technical lignins significantly, thereby overcoming a serious obstacle to their applicability.