ATAD3B is a mitophagy receptor mediating clearance of oxidative stress-induced damaged mitochondrial DNA.

Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.

Single-Cell RNA Sequencing Deconstructs the Distribution of Immune Cells Within Abdominal Aortic Aneurysms in Mice.

BACKGROUND: Inflammation is a key component in the development of abdominal aortic aneurysm (AAA), yet insights into the roles of immune cells and their interactions in this process are limited. METHODS: Using single-cell RNA transcriptomic analysis, we deconstructed the CD45+ cell population in elastase-induced murine AAA at the single-cell level. We isolated each group of immune cells from murine AAA tissue at different time points and divided them into several subtypes, listed the remarkable differentially expressed genes, explored the developmental trajectories of immune cells, and demonstrated the interactions among them. RESULTS: Our findings reveal significant differences in several immune cell subsets, including macrophages, dendritic cells, and T cells, within the AAA microenvironment compared with the normal aorta. Especially, conventional dendritic cell type 1 exclusively existed in the AAA tissue rather than the normal aortas. Via CellChat analysis, we identified several intercellular communication pathways like visfatin, which targets monocyte differentiation and neutrophil extracellular trap-mediated interaction between neutrophils and dendritic cells, which might contribute to AAA development. Some of these pathways were validated in human AAA. CONCLUSIONS: Despite the absence of external pathogenic stimuli, AAA tissues develop a complex inflammatory microenvironment involving numerous immune cells. In-depth studies of the inflammatory network shall provide new strategies for patients with AAA.

Rhodium-Catalyzed Asymmetric C-H Functionalization Reactions.

This review summarizes the advancements in rhodium-catalyzed asymmetric C-H functionalization reactions during the last two decades. Parallel to the rapidly developed palladium catalysis, rhodium catalysis has attracted extensive attention because of its unique reactivity and selectivity in asymmetric C-H functionalization reactions. In recent years, Rh-catalyzed asymmetric C-H functionalization reactions have been significantly developed in many respects, including catalyst design, reaction development, mechanistic investigation, and application in the synthesis of complex functional molecules. This review presents an explicit outline of catalysts and ligands, mechanism, the scope of coupling reagents, and applications.

Chiral Brønsted Acid-Catalyzed Intramolecular Asymmetric Dearomatization Reaction of Indoles with Cyclobutanones via Cascade Friedel-Crafts/Semipinacol Rearrangement.

The highly efficient synthesis of chiral indolines fused with an azabicyclo[2.2.1]heptanone moiety is achieved by an asymmetric dearomatization reaction of indoles with cyclobutanones. A new chiral imidodiphosphorimidate (IDPi) catalyst is synthesized and exhibits extraordinary activity in promoting a cascade Friedel-Crafts/semipinacol rearrangement. Target molecules are prepared in good yields (up to 95%) with excellent enantioselectivity (up to 98% ee) with operational convenience. Combined experimental and computational studies provide detailed mechanistic insights into the energy landscape and origin of the stereochemical induction of the reaction.

Z-Retentive Asymmetric Allylic Substitution Reactions of Aldimine Esters under Ru/Cu Dual Catalysis.

Ru/Cu dual catalysis has been applied for Z-retentive asymmetric allylic substitution reactions of aldimine esters. This reaction provides an enantioselective synthesis of chiral Z-olefins in high yields (up to 91% yield) with excellent enantioselectivity (up to 98% ee) under mild conditions. The previously unreacted trisubstituted allylic electrophiles under Ir catalytic system are found to be compatible, affording the stereoretentive products in either Z- or E-form. Both linear and branched allylic electrophiles are suitable substrates with excellent reaction outcomes. Notably, Ru and Cu complexes are added in one-pot and simplifies the manipulation of this protocol and self-sorting phenomena could be observed in this Ru/Cu dual catalytic system.

Chiral Bis(binaphthyl) Cyclopentadienyl Ligands for Rhodium-Catalyzed Desymmetrization of Diarylmethanes via Selective Arene Coordination.

Owing to substantial advances in the past several decades, transition-metal-catalyzed asymmetric reactions have garnered considerable attention as pivotal methods for constructing chiral molecules from abundant, readily available achiral counterparts. These advances are largely attributed to the development of chiral ligands that control stereochemistry through steric repulsion and other noncovalent interactions between the ligands and functional groups or prochiral centers on the substrates. However, stereocontrol weakens dramatically with increasing distance between the reaction site and the functional group or prochiral center. Herein, we report a symphonic strategy for remote stereocontrol of Rh(III)-catalyzed asymmetric benzylic C-H bond addition reactions of diarylmethanes in which the two aryl motifs differ at the meta and/or para position. Specifically, catalysts bearing a new type of chiral cyclopentadienyl (Cp) ligand differentiate between the two aromatic rings of the diarylmethane by arene-selective η6 coordination, setting up an opportunity for ligand-controlled stereoselective benzylic deprotonation and subsequent stereoselective addition to the 1,1-bis(arylsulfonyl)ethylene.

Gd(III)-Catalyzed Regio-, Diastereo-, and Enantioselective [4 + 2] Photocycloaddition of Naphthalene Derivatives.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

Novel dominant and recessive variants in human ROBO1 cause distinct neurodevelopmental defects through different mechanisms.

The Roundabout (Robo) receptors, located on growth cones of neurons, induce axon repulsion in response to the extracellular ligand Slit. The Robo family of proteins controls midline crossing of commissural neurons during development in flies. Mono- and bi-allelic variants in human ROBO1 (HGNC: 10249) have been associated with incomplete penetrance and variable expressivity for a breath of phenotypes, including neurodevelopmental defects such as strabismus, pituitary defects, intellectual impairment, as well as defects in heart and kidney. Here, we report two novel ROBO1 variants associated with very distinct phenotypes. A homozygous missense p.S1522L variant in three affected siblings with nystagmus; and a monoallelic de novo p.D422G variant in a proband who presented with early-onset epileptic encephalopathy. We modeled these variants in Drosophila and first generated a null allele by inserting a CRIMIC T2A-GAL4 in an intron. Flies that lack robo1 exhibit reduced viability but have very severe midline crossing defects in the central nervous system. The fly wild-type cDNA driven by T2A-Gal4 partially rescues both defects. Overexpression of the human reference ROBO1 with T2A-GAL4 is toxic and reduces viability, whereas the recessive p.S1522L variant is less toxic, suggesting that it is a partial loss-of-function allele. In contrast, the dominant variant in fly robo1 (p.D413G) affects protein localization, impairs axonal guidance activity and induces mild phototransduction defects, suggesting that it is a neomorphic allele. In summary, our studies expand the phenotypic spectrum associated with ROBO1 variant alleles.

Site-Specific Anchoring a Luminescent Tag in a Protein with Non-Emissive Iridium(III) Complex.

Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N)2 (H2 O)2 ]+ OTF- (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix. Replacement of the two labile water ligands in the iridium(III) complex by a protein HisHis pair increases the luminescent intensity up to over 100 folds. This labeling approach has been demonstrated in a highly specific and efficient manner in a number of proteins, and it is also feasible for labeling target proteins in cell lysates.

Novel intertypic recombination of Echovirus 11 in the Enterovirus species B.

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.

Glucose metabolism disorder related to follicular fluid exosomal miR-122-5p in cumulus cells of endometriosis patients.

In Brief: Elevated expression of miR-122-5p in exosomes in the follicular fluid of patients with endometriosis impairs glucose metabolism in cumulus cells and may further impair oocyte quality. Abstract: Endometriosis (EMs) affects fertility in women of childbearing age in many ways. The underlying mechanisms, including the decrease in oocyte quality, require further investigation. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, including follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aimed to elucidate the mechanisms involved in EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST), and the control group (Ctrl). Mouse cumulus-oocyte complexes (COCs) were co-cultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG human ovarian granulosa cells transfected with an miRNA mimic and inhibitor. It was found that the follicular fluid exosomes from patients with untreated EMs reduced both the rate of maturation and the quality of mouse oocytes. Overexpression of miR-122-5p in untreated EMs inhibited the translation of key aldolase enzymes related to glucose metabolism and partly impaired glucose metabolism in the cumulus cells of patients with endometriosis. miR-122-5p was also observed to reduce proliferation and increase apoptosis after cell transfection with an miR-122-5p mimic and inhibitor. Further experiments are needed to determine whether there are additional small molecules in the follicular fluid of patients with endometriosis that could be involved in damaging oocyte quality and to identify where harmful substances in follicular fluid exosomes are loaded.

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 µg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 µg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Risk of Dementia in Different Types of Cancer Survivors: A Nationwide Cohort Study.

OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.

Electrophile-Arene Affinity: An Energy Scale for Evaluating the Thermodynamics of Electrophilic Dearomatization Reactions.

Rational design and development of organic reactions are lofty goals in synthetic chemistry. Quantitative description of the properties of molecules and reactions by physical organic parameters plays an important role in this regard. In this Article, we report an energy scale, namely, electrophile-arene affinity (EAA), for evaluating the thermodynamics of electrophilic dearomatization reactions, a class of important transformations that can rapidly build up molecular complexity and structural diversity by converting planar aromatic compounds into three-dimensional cyclic molecules. The acquisition of EAA data can be readily achieved by theoretically calculating the enthalpy changes (ΔH) of the hypothetical reactions of various (cationic) electrophiles with aromatic systems (taking the 1-methylnaphthalen-2-olate ion as an example in this study). Linear correlations are found between the calculated ΔH values and established physical organic parameters such as the percentage of buried volume %VBur (steric effect), Hammett's σ or Brown's σ+ (electronic effect), and Mayr's E (reaction kinetics). Careful analysis of the ΔH values leads to the rational design of a dearomative alkynylation reaction using alkynyl hypervalent iodonium reagents as the electrophiles.

Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor.

STUDY OBJECTIVE: To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN: A retrospective cohort study. SETTING: This study was conducted at a tertiary referral center. PATIENTS: A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS: Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS: In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION: This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.

Prophylactic use of vancomycin powder on postoperative infection after total joint arthroplasty.

OBJECTIVE: By reviewing the literature analyzing vancomycin powder for preventive surgery, the effect of this method on reducing the infection rate after TJA was systematically evaluated to provide a basis for future clinical work. METHODS: Using PubMed, Medline, Elsevier, and CNKI, with the following mesh words: "vancomycin", "local / intraoperative / topical / intrawound", "TJA", "TKA", "THA", "total joint arthroplasty", "total knee arthroplasty", "total hip arthroplasty", "infection", and "SSI", to search for case-control research papers on the impact of prophylactic application of vancomycin powder on the incidence of postoperative infection, we compared the overall infection rate in the literature by using RevMan 5.3 meta-analysis software and analyzed the impact of vancomycin on the infection rate of different parts and types of TJA according to different subgroups. RESULTS: A total of 22 qualified studies were selected; twenty-five studies compared the effect of prophylactic use of vancomycin powder on infection rates after TJA. There were 23,363 cases in total, including 9545 cases in the vancomycin group and 13,818 cases in the control group. The results of the meta-analysis showed that the possibility of postoperative infection after prophylactic use of vancomycin powder was significantly lower than that without vancomycin risk ratio: 0.38 [0.23,0.59], P < 0.01). However, a meta-analysis of randomized controlled trials (RCTs) showed no significant effect of vancomycin on postoperative infection (P = 0.52). CONCLUSION: Based on the retrospective studies, local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection. High-quality RCTs should be carried out to further evaluate these results.

Alkaloids from Fritillaria przewalskii Bulbs and Their Anti-Alzheimer's Disease Activities.

Three undescribed isosteroidal alkaloids, przewalskines A-C (1-3), as well as seven known alkaloids (4-10) were obtained from Fritillaria przewalskii bulbs. Their structures were deduced by extensive HRESIMS, 1D NMR, and 2D NMR analyses, and their bioactivities were evaluated involving the anti-inflammatory and inhibitory potencies on AChE, BChE, and Aß aggregation. Compound 4 revealed the potent effect on inhibiting Aß aggregation activity with IC50 value of 33.1 µM, AChE activity with IC50 value of 6.9 µM, and also showed NO release inhibitory acitivity with IC50 value of 32.6 µM. These findings contribute new multi-.target anti-AD agents and embody the chemical diversity of F. przewalskii.

Cross-cultural translation and validation of the Chinese version Distress Tolerance Scale for adolescents with chronic physical disease.

INTRODUCTION: Chronic physical disease (CPD) makes life filled with many negative events in adolescents, but not all adolescents experiencing negative life events proceed to develop emotional distress, only those with low emotional distress tolerance (EDT). A valid and reliable scale to measure EDT in CPD adolescents is important for caring for their emotional distress. Therefore, the purpose of this study is to translate the 15-item English version Distress Tolerance Scale (DTS) into a Chinese version and then validate the scale for measuring EDT of adolescents with CPD. METHODS: The 15-item English version DTS was translated into a Chinese version using the translation guidelines for cross-cultural research. Two cohorts of adolescents with CPD were recruited from four hospitals in southern Taiwan, with the first cohort including 124 adolescents with CPD employed to conduct exploratory factor analysis, corrected item-total correlation and reliability testing, while the second cohort, consisting of 238 adolescents with CPD, was utilized to examine confirmatory factor analysis and concurrent validity. RESULTS: The two-factor nine-item Chinese version DTS for Adolescents with CPD (C-DTS-A) was developed. Lower scores of the C-DTS-A were significantly associated with higher diabetes distress, poorer self-management, and worse glycaemic control; their correlation coefficients sequentially were -.40, .17 and -.23. Cronbach's α and the test-retest reliability of the two-factor C-DTS-A ranged from .81 to .87 and from .79 to .89, respectively. CONCLUSION: The two-factor nine-item C-DTS-A with good cross-cultural translation quality was a reliable and valid scale to assess EDT for adolescents with CPD.

The Inhibiting Effect of GB-2, (+)-Catechin, Theaflavin, and Theaflavin 3-Gallate on Interaction between ACE2 and SARS-CoV-2 EG.5.1 and HV.1 Variants.

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose significant global health challenges. The results demonstrated that GB-2 at 200 µg/mL effectively increased the population of 293T-ACE2 cells with low RBD binding for both SARS-CoV-2 Omicron EG.5.1 and HV.1 variants by dual-color flow cytometry, indicating its ability to inhibit virus attachment. Further investigation revealed that (+)-catechin at 25 and 50 µg/mL did not significantly alter the ACE2-RBD interaction for the EG.5.1 variant. In contrast, theaflavin showed inhibitory effects at both 25 and 50 µg/mL for EG.5.1, while only the higher concentration was effective for HV.1. Notably, theaflavin 3-gallate exhibited a potent inhibition of ACE2-RBD binding for both variants at both concentrations tested. Molecular docking studies provided insight into the binding mechanisms of theaflavin and theaflavin 3-gallate with the RBD of EG.5.1 and HV.1 variants. Both compounds showed favorable docking scores, with theaflavin 3-gallate demonstrating slightly lower scores (-8 kcal/mol) compared to theaflavin (-7 kcal/mol) for both variants. These results suggest stable interactions between the compounds and key residues in the RBD, potentially explaining their inhibitory effects on virus attachment. In conclusion, GB-2, theaflavin, and theaflavin 3-gallate demonstrate significant potential as inhibitors of the ACE2-RBD interaction in Omicron variants, highlighting their therapeutic promise against COVID-19. However, these findings are primarily based on computational and in vitro studies, necessitating further in vivo research and clinical trials to confirm their efficacy and safety in humans.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon-Carbon Coupling Techniques.

This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C-C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C-H-activation, and facilitating cycloaddition and C-S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C-C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.