Reagents Research Articles

Applicability of few layer graphene derived from annoni grass biomass on the mechanical properties of cement mortars

In this work, we report the potential applicability of few layer graphene (FLG) synthesized from annoni grass (AG) biomass (Eragrostis plana Nees) by investigating its impact on the flexural and compression strength of cement mortars. For this purpose the AG biomass was collected and burnt at the temperature of 400 °C per 60 min, obtaining the AG ash (AGA). For FLG production, the AGA was mixture with the chemical reagent potassium hydroxide (KOH) and burnt at the temperature and time of 850 °C and 60 min, respectively. For the mechanical properties analysis, a reference sample (A0-without FLG) and samples with different percentage of FLG were prepared, specifically 0.02 % (A1), 0.03 % (A2), 0.05 % (A3), 0.07 % (A4) and 0.1 % (A5). Statistical analysis (Analysis of Variance, ANOVA) of the mechanical properties demonstrates a maximum flexural and compression strength in sample A2. The flexural and compression strength increase 25.2 % and 10.1 % compared to the reference mortar. These results indicate that the FLG produced from AG not only improves the mechanical properties of mortars but also presents significant environmental benefits, because AG is considered an invasive pest of agricultural fields of the southern region of Brazil. Therefore, with its removal from the fields it would be contributing to environmental preservation.

Discovery and Characterization of BAY-184: A New Potent and Selective Acylsulfonamide-Benzofuran In Vivo-Active KAT6AB Inhibitor.

KAT6A and KAT6B genes are two closely related lysine acetyltransferases that transfer an acetyl group from acetyl coenzyme A (AcCoA) to lysine residues of target histone substrates, hence playing a key role in chromatin regulation. KAT6A and KAT6B genes are frequently amplified in various cancer types. In breast cancer, the 8p11-p12 amplicon occurs in 12-15% of cases, resulting in elevated copy numbers and expression levels of chromatin modifiers like KAT6A. Here, we report the discovery of a new acylsulfonamide-benzofuran series as a novel structural class for KAT6A/B inhibition. These compounds were identified through high-throughput screening and subsequently optimized using molecular modeling and cocrystal structure determination. The final tool compound, BAY-184 (29), was successfully validated in an in vivo proof-of-concept study.

The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis.

Inhibition of integrin αvβ6 is a promising approach to the treatment of fibrotic disease such as idiopathic pulmonary fibrosis. Screening a small library combining head groups that stabilize the bent-closed conformation of integrin αIIbβ3 with αv integrin binding motifs resulted in the identification of hit compounds that bind the bent-closed conformation of αvβ6. Crystal structures of these compounds bound to αvβ6 and related integrins revealed opportunities to increase potency and selectivity, and these efforts were accelerated using accurate free energy perturbation (FEP+) calculations. Optimization of PK parameters including permeability, bioavailability, clearance, and half-life resulted in the discovery of development candidate MORF-627, a highly selective inhibitor of αvβ6 that stabilizes the bent-closed conformation and has good oral PK. Unfortunately, the compound showed toxicity in a 28-day NHP safety study, precluding further development. Nevertheless, MORF-627 is a useful tool compound for studying the biology of integrin αvβ6.

Discovery of Potent and Selective Blockers Targeting the Epilepsy-Associated KNa1.1 Channel.

Gain-of-function (GOF) mutations of the sodium-activated potassium channel KNa1.1 (Slack, Slo2.2, or KCa4.1) induce severe, drug-resistant forms of epilepsy in infants and children. Although quinidine has shown promise in treating KCNT1-related epilepsies compared to other drugs, its limited efficacy and substantial side effects necessitate the development of new KNa1.1 channel inhibitors. In this study, we developed a novel class of KNa1.1 inhibitors using combined silico approaches and structural optimization. Among these inhibitors, compound Z05 was identified as a selective potential KNa1.1 inhibitor, especially against the hERG channel. Moreover, its binding site and potential counteraction to a GOF mutant Y796H were identified by the mutation studies. Our data also showed that Z05 had significant pharmacological profiles, including high brain penetration and moderate oral bioavailability, offering a valuable in vitro tool compound for further drug development in treating KCNT1-related epilepsies.

A Rapid Analysis Method for Determination of Hydrocarbon Types in Aviation Turbine Fuel by Gas Chromatography-Mass Spectrometry.

A rapid analysis method for determination of hydrocarbon types in aviation turbine fuel was investigated in this study. A kind of reversible adsorption material packed as an unsaturated trap was used to separate saturated hydrocarbons and unsaturated hydrocarbons in the GC-MS system. No manual process or organic reagent was needed during the entire analysis process. The contents of 13 kinds of hydrocarbons, including paraffins, monocycloparaffins, dicycloparaffins, tricycloparaffins, monoolefins, cycloolefins, alkylbenzenes, CnH2n-8 aromatics, CnH2n-10 aromatics, naphthalenes, CnH2n-14 aromatics, CnH2n-16 aromatics, and CnH2n-18 aromatics were calculated by the characteristic mass fragments detected by MS with the modified matrices of ASTM D2425. The overall analysis time was less than 10 min. The precision of this test method has been conducted with 8 laboratories attended and 16 samples analyzed. The performance of this new method was demonstrated by comparing the results tested by ASTM D1319, ASTM D2425, and ASTM D6379. This rapid analysis method can provide hydrocarbon compositions of aviation turbine fuels or other liquid hydrocarbon samples within the same distillation range.

Molecular Engineering Chemical Pre-lithiation Reagent with Low Redox Potential for Graphite Anode Enables High Coulombic Efficiency.

Graphite (Gr) is a low-cost and high-stability anode for lithium-ion batteries (LIBs). However, Gr anode exhibits an obstinate drawback of low initial Coulombic efficiency (ICE), owing to the active lithium loss for the solid electrolyte interphase (SEI) layer. Herein, a straightforward and effective chemical pre-lithiation strategy is proposed to compensate for the lithium loss. A molecular engineering phenanthrene-based lithium-arene complex (Ph-based LAC) reagent is designed by density functional theory (DFT) calculations. The engineering Ph-based reagent enhances the stability of the π-electron system and the electron-donating capacity, resulting in a reduced redox potential to facilitate lithium transfer. The electrochemical distinct of the Ph-based reagent is illustrated, the prelithiation process in a low Li-insertion platform, and the lithiation degree is controllable with the dipping time (ICE = 102%, 3min). Notably, a denser and homogeneous SEI layer has pre-formed to enhance the Li+ transport and interface stability. Moreover, the lithium-ion full batteries assemble with LiFePO4 and NCM811 cathode, which exhibits high ICE (96.5% and 90.3%) and energy density (310 and 333Whkg-1). These findings present a facile and controllable pre-lithiation strategy to compensate for the lithium of LIBs, providing new valuable insights into the design and optimization of battery manufacture.

Catalytic Strategies for the Selective Synthesis of α‐ and β‐Functionalized Amines via Hydrofunctionalization of Enamides

α‐ and β‐functionalized amines are two classes of important compounds, whose structural units are widely present in approved drugs. The hydrofunctionalization of enamides is the most direct and efficient method for constructing these two types of compounds. The regioselectivity was the focus of this conversion, which is largely influenced by the catalytic mode. Therefore, in order to selectively synthesize α‐ or β‐functionalized amines, the progress in catalytic hydrofunctionalization of enamides over the past decade are reviewed, and the catalytic pathways for the hydrofunctionalization of enamides are discussed in detail. This account aims to objectively evaluate the effects of various catalytic pathways on the regioselectivity of hydrofunctionalization, in order to provide a new perspective on the selection of catalytic methods and the design of catalytic pathways for selective synthesis α‐ or β‐functionalized amines. This review has been divided into the following sections: 1. Introduction 2. Organic reagents catalysis 3. Transition metal catalysis 4. Photoredox catalysis 5. Summary and prospect Keywords: α‐ and β‐functionalized amines; enamides; regioselectivity; hydrofunctionalization; catalytic strategies

Evaluation of STK17B as a cancer immunotherapy target utilizing highly potent and selective small molecule inhibitors

IntroductionThe serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy.MethodsTo assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed into a flow cytometry-based pharmacodynamic readout of STK17B inhibition both in vitro and in vivo.ResultsIn a mouse T cell activation assay, STK17B inhibitors demonstrated the ability to enhance interleukin-2 (IL-2) production. Similarly, treatment with STK17B inhibitors resulted in stronger cytokine secretion in human T cells activated using a T cell bispecific antibody. Subsequent chemistry optimization led to the identification of a highly selective and orally bioavailable tool compound, BLU7482. In vivo, STK17B inhibition led to dose-dependent modulation of myosin light chain 2 phosphorylation and enhanced priming of naïve T cells, as determined by upregulation of CD69, IL-2 and interferon-γ secretion. In line with increased T cell activation, treatment with STK17B inhibitor enhanced antitumor activity of anti–PD-L1 antibody in the MCA205 model.ConclusionsIn summary, we successfully identified and optimized STK17B kinase inhibitors which led to increased T cell responses in vitro and in vivo. This allowed us to evaluate the potential of STK17B inhibition as an approach for cancer immunotherapy.

IL-6 and INF-γ Mediated Immune Responses in Mice Induced by Campylobacter jejuni Bacterial Ghosts

Background: Bacterial ghosts (BGs) a growing interest in their potential medical and pharmacological uses in recent years which is just. The empty bacterial envelopes Absent its internal substance .in this study using BGs for campylobacter jejuni which is curved, non- spore -forming, gram -negative rods that measure approximately 0.2 to 0.9µ₥×0.5 to 5.0 µ₥. Enteric campylobacter may appear as long spirals or S-or seagull -wing shapes. these organisms may appear as coccobacilli in smears prepared older cultures. Methods: On gram stained smears, these organisms stain poorly for better visualization carbol- fuchsin is recommended as a counterstain, if safranin is used, counterstaining should be extended to 2 to 3 minutes campylobacter spp. is motil. There are two methods for preparation of (BGs) either by E-lysis gene creating a lysis tunnel structure inside the active bacteria's envelope. Or by using minimum inhibition concentration and minimum growth concentration for chemical compounds (MIC), (MGC) in a row. The ideal circumstances for the generation of BGs were mapped using the Plackett-Burman experimental design using two experimental. Results: A spectrophotometer was used to measure the amount of DNA and protein released. The whole experiment was divided into three steps: in the first step all the chemical reagents except H2O2 were added to bacterial suspension, in the second step only H2O2, and in the third step, the cell pellets reconstituted in 60% ethanol and kept at room temperature for thirty minutes with gentle swirl of the cells for thirty seconds every five minutes. Cell pellets were gathered and cleaned again using the same procedure as mentioned. It was assured that no living cells were left behind in the bacterial spoon by cultivation using N.B. after the experiment. The lab animal Mic injected with BG from Campylobacter jejuni as a vaccine 28 days from the last immunization, which used the qPCR technique for the immune test, has been chosen. IL-6 and INF-G for this test. Conclusion: The immune responses accorded as a result of giving the vaccine was obtained from this the results of this research.

Blocking endogenous phosphorus release in sediments by a hydrotalcite mixture synthesized with natural sepiolite and discarded cans

Pure hydrotalcite (LDH) materials prepared from chemical reagents have been investigated as solid-phase phosphorus (P) inactivation materials (SPIM) to manage endogenous P loading in sediments. However, the efficacy and mechanism of LDH mixtures prepared by natural minerals and solid wastes in controlling sediment P release are unclear. Therefore, a Ca/Mg-Al-LDH (CMA-LDH) material was synthesized using sepiolite and cans, and its efficacy, mechanism, and ecological impact in controlling sediment P release were investigated. CMA-LDH-p was prepared as a control material using pure chemical reagents. The CMA-LDH and CMA-LDH-p were both composed of hydrotalcite and hydrocalumite. The maximum P adsorption capacity of CMA-LDH was 123.01 mg/g, comparable to that of CMA-LDH-p. The adsorbed P by CMA-LDH was mostly in the stable P form, accounting for 87.2 % of the total P. The adsorption capacity and immobilization ability of CMA-LDH for P were superior to other reported LDH-based SPIM. Both the CMA-LDH addition and capping successfully blocked sediment P release under anaerobic conditions. Passivation of mobile P in the sediment and DGT-labile P in the interstitial water was critical to preventing sediment P release by the CMA-LDH addition. The CMA-LDH capping inhibited sediment P release through the effective adsorption of CMA-LDH on DGT-labile P at the sediment/overlying water interface. The CMA-LDH addition and capping affected the abundance of microbial communities associated with iron and sulfur cycling, which might affect the stability of endogenous P. These results confirmed that CMA-LDH addition and capping treatments were effective methods for managing sediment P loading.

Treatment and Recycling of Tungsten Beneficiation Wastewater: A Review

The large amount of wastewater containing various pollutants generated during the tungsten beneficiation process has become a bottleneck for the sustainable development of tungsten mining enterprises. Typical pollutants mainly include suspended solids (SSs), silicate ions, metal ions, and residual organic reagents. The direct discharge of untreated tungsten beneficiation wastewater can cause serious harm to the ecological environment, while recycling can significantly affect flotation indicators. In this paper, the sources and characteristics of typical pollutants were analyzed, and various purification techniques were outlined, including coagulation, adsorption, chemical precipitation, oxidation, and biological treatment methods. Among these techniques, coagulation is particularly effective for the removal of SSs, while adsorption and chemical precipitation are recommended for the removal of soluble ions. For residual organic reagents, oxidation methods have demonstrated high treatment efficiencies. The mainstream methods for wastewater recycling were summarized, including centralized recycling, as well as internal recycling at certain stages. For tungsten beneficiation such a complex process, where the quality of wastewater varies greatly between different stages, it is suitable to recycle the wastewater after appropriate treatment at a specific stage. Furthermore, this study provided a perspective on the future directions of tungsten beneficiation wastewater treatment, serving as a reference for related research and industrial practices.

CaCO3-activited N-doped diatom biochar for the degradation of tetracycline

In this study, a N-doped diatom biochar (DBC) was prepared by one-step pyrolysis, where CaCO3 formed by marine diatom-mediated calcification was employed as an activator. Due to the activation effect of CaCO3, the specific surface area of the obtained DBC increased by more than 10 times, and the nitrogen presented as pyrrolic nitrogen (58.9%), pyridinic nitrogen (29.7%), and graphitic nitrogen (11.4%) in the DBC. In addition, the effects of important parameters and co-existing ions on the catalytic decomposition of tetracycline (TC) by DBC were investigated by using TC as a typical pollutant and PDS as an oxidant. The DBC/PDS system exhibited high activity over a broad pH range. Through radical scavenging experiments, electron spin resonance, and electrochemical results analysis, it was found that the degradation of TC in the system included both radical and nonradical pathways, and the most dominant reactive species was 1O2. Furthermore, the surficial reactive complexes formed by PDS on the catalysts also played an important role in attacking the adsorbed TC molecules. This study proposes an eco-friendly and economical technique to construct a clean advanced oxidation process capable of treating TC wastewater by utilizing the native biomass of diatom as a metal-free and efficient biochar catalyst while simultaneously reducing the use of chemical reagents.

A cross-disease resource of living human microglia identifies disease-enriched subsets and tool compounds recapitulating microglial states.

Human microglia play a pivotal role in neurological diseases, but we still have an incomplete understanding of microglial heterogeneity, which limits the development of targeted therapies directly modulating their state or function. Here, we use single-cell RNA sequencing to profile 215,680 live human microglia from 74 donors across diverse neurological diseases and CNS regions. We observe a central divide between oxidative and heterocyclic metabolism and identify microglial subsets associated with antigen presentation, motility and proliferation. Specific subsets are enriched in susceptibility genes for neurodegenerative diseases or the disease-associated microglial signature. We validate subtypes in situ with an RNAscope-immunofluorescence pipeline and high-dimensional MERFISH. We also leverage our dataset as a classification resource, finding that induced pluripotent stem cell model systems capture substantial in vivo heterogeneity. Finally, we identify and validate compounds that recapitulate certain subtypes in vitro, including camptothecin, which downregulates the signature of disease-enriched subtypes and upregulates a signature previously associated with Alzheimer's disease.

Using Microplates to Test Boron in Zea mays Leaf Plant and the Surrounding Soil

Background: Boron plays a crucial role in cell wall construction in plants and also facilitates the transfer of carbohydrates, which are essential for various physiological processes. The objective was to measure element concentrations in soil, water extracts and plant tissues (Zea mays) using Azomethine-H and ICP-MS within a controlled microplate assay. Methods: A microscopic plate repeat test was used to analyze the concentration of boron in soil extracts and plant tissue ash from local Zea mays leaves, considering the global trend in environmental sustainability. Tests aimed to modify the azomethine-H microscopic approach to eliminate pH and chemical interferences in soil samples and plant tissues. Due to their ability to ensure sample repeatability and quality control, micro spectrophotometers are ideal for high-throughput analysis. Result: The microplate test has enhanced boron measurement in soil and plant tissue samples. Our improvements to the microplate B assay have resulted in more accurate boron measurements in these samples. Microplate B testing is effective and suitable analysis in modern research and laboratories, using 40 times less chemical reagent per sample than traditional spectrophotometry. Additionally, microplates enable simultaneous analysis and calibration of samples. The modified plate test significantly improves boron measurement in soil and plant tissue samples, using 40 times fewer reagents than traditional spectrophotometry. This method is cost-effective, ideal research, commercial analysis and making it a valuable tool for modern laboratories.

Precise Immobilization Strategy Combined with Rational Design to Improve β-Agarase Stability.

Recently, the orientational immobilization of enzymes has attracted extensive attention. In this study, we report the development of a strategy combined with rational design to achieve precise site-specific covalent immobilization of β-agarase. We first rationally screened six surface sites that can be mutated to cysteine by combining molecular dynamics simulation and energy calculation. Site-specific immobilization was successfully achieved by Michael addition reaction of mutant enzymes and maleimide-modified magnetic nanoparticles (MAL-MNPs). The enzyme activity retention rate of R66C-MAL-MNPs and K588C-MAL-MNPs was greater than 96%. The thermal deactivation kinetics study revealed that the site-specific immobilization strategy significantly improved the thermal stability of Aga50D, resulting in a substantial increase in its antidenaturation activity at elevated temperatures, and the highest t1/2 of the immobilized mutant enzymes was increased by an impressive 21.25-fold at 40 °C. The immobilized mutant enzymes also showed significantly enhanced tolerance to metal ions and organic reagents. For instance, all of the immobilized enzymes maintained over 90% of their enzymatic activity in the 50% (v/v) acetone/water solution. The present work may pave the way for the design of precisely immobilized enzymes, which can help promote green manufacturing.

Deep silicification–assisted long-term preservation of structural and genomic information across biospecies: From micro to macro

The concurrent preservation of morphological, structural, and genomic attributes within biological samples is paramount for comprehensive insights into biological phenomena and disease mechanisms. However, current preservation methodologies (e.g., cryopreservation, chemical reagent fixation, and bioplasticization) exhibit limitations in simultaneously achieving these critical combined goals. To address this gap, inspired by natural fossilization, here we propose "deep silicification," a room temperature technology that eliminates fixation requirements and overcomes the cold chain problem. By harnessing the synergy between ethanol and dimethyl sulfoxide, deep silicification significantly enhances silica penetration and accumulation within bioorganisms, thereby reinforcing structural integrity. This versatile and cost-effective approach demonstrates remarkable efficacy in preserving organismal morphology across various scales. Accelerated aging experiments underscore a 4,723-fold enhancement in genomic information storage over millennia, with whole-genome sequencing confirming nearly 100% fidelity. With its simplicity and reliability, "deep silicification" represents a paradigm shift in biological sample storage.

Eco-Friendly Facile Conversion of Waste Eggshells into CaO Nanoparticles for Environmental Applications.

Amongst the many types of food waste, eggshells contain various minerals and bioactive materials, and they can become hazardous if not properly disposed of. However, they can be made useful for the environment and people by being converted to environmentally friendly catalytic materials or environmental purification agents. Simple calcination can enhance their properties and thereby render them suitable for catalytic and environmental applications. This work aimed to prepare CaO from waste eggshells and examine its effectiveness in photocatalytic pollution remediation, electrocatalytic activity, optical sensing, and antibacterial activities. As opposed to other techniques, this calcination process does not require any chemical reagents due to the high purity of CaCO3 in eggshells. Calcium oxide nanoparticles were prepared by subjecting waste eggshells (ES) to high-temperature calcination, and the synthesized CaO nanoparticles were characterized for their structural, morphological, chemical, optical, and other properties. Furthermore, their photocatalytic degradation of methylene blue dye and antibacterial efficiency against Escherichia coli and Staphylococcus aureus were investigated. It was found that the green-converted CaO can be efficiently used in environmental applications, showing good catalytic properties.

Constructing boosted charge separation for efficient H2O2 production and pollutant degradation by highly defective ZnIn2S4/ carbon doped boron nitride

Solar-driven photocatalytic production of H2O2 as a promising environmentally-friendly approach has been applied as a chemical reagent and for enhancing photocatalytic remediation. However, this process is still limited by unsatisfactory efficiency and hard separation of photogenerated charge carriers. Herein, we design a dual pathway to improve hydrogen peroxide production by establishing a 2D/2D heterojunction between carbon-doped boron nitride (BCN) and defective zinc indium sulfide (ZIS). The introduction of multiple vacancies and dopants at the interface successfully promoted the interfacial charge transfer and peroxide generation. The Z-scheme heterojunction establishes a built-in electronic field, facilitating continuous electron accumulation and depletion, thereby inducing band bending. As a result, the optimized BCN/ZIS-30 composite (>420 nm wavelength) exhibits 925 μmol/g/h in pure water with no other additions and advances this production to 2006.1 μmol/g/h (2 times as defective ZIS and 12.1 times as BCN) under the existence of isopropanol and aeration. Mechanism investigation indicated that H2O2 is generated via a two-step electron reduction route and water oxidation reaction. The generated H2O2 successfully constructs a self-photo-Fenton system by forming hydroxyl radicals. Accompanied by strong oxygen activation ability, the photo-Fenton system also exhibits rapid degradation of antibiotics with 95 % elimination in 60 minutes. The practical applicability of this photocatalyst was demonstrated through real water remediation tests, exhibiting its effectiveness in removing antibiotics, COD, and total ammonia nitrogen, highlighting its potential for practical water treatment applications. This work provides a novel idea on constructing heterojunction materials for energy saving and water remediation.

Rapid and highly sensitive detection of trace chromium and copper in tea infusion using laser-induced breakdown spectroscopy combined with electrospinning technology

Tea infusion, as one of the most popular beverages, is favored by people around the world. However, tea plants accumulate heavy metals from the soil during growth, which are gradually transferred to the leaves and subsequently decomposed into the tea infusion after soaking in hot water. Long-term consumption of tea infusion containing heavy metals may lead to severe health issues, such as liver dysfunction and cancer. Therefore, rapid, precise, and highly sensitive detection of heavy metals in tea infusion becomes crucial for human health. Traditional methods, such as atomic absorption spectroscopy (AAS), suffer from long detection cycles, high costs, and the risk of secondary pollution from chemical extraction reagents. Thus, this paper presents a method, using laser-induced breakdown spectroscopy combined with electrospinning technology (LIBS-ES), to detect trace amounts of Cr and Cu in tea infusion. The electrospun nanofiber membranes (ENM) were modified with gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs), achieving ultra-sensitive detection of Cr and Cu. The experiment results show that the limits of detection for Cr and Cu are 5 μg/L and 10 μg/L, respectively. Moreover, this method was successfully applied to the detection of Cr and Cu in seven different types of tea infusion, achieving recovery rates of 99 %-106 % and 99 %-108 %, respectively. The method demonstrated good performance even under the interference of other ions at various concentrations, providing a reference for the rapid and highly sensitive detection of heavy metals in tea infusion.

Photoelectrocatalytic [4+2] Annulation for S-Heterocycle Assembly Enabled by Proton-Coupled Electron Transfer (PCET).

Cross-dehydrogenative couplings (CDC) present an efficient strategy for the assembly of biorelevant heterocycles, but are thus far largely limited to toxic transition metals and rather harsh reaction conditions. In sharp contrast, we, herein report on a mild photoelectrocatalyzed CDC-[4+2] annulation enabling the synthesis of functionalized isothiochromenes enabled by a proton-coupled electron transfer (PCET) strategy. The transformative photoelectrocatalysis obviated toxic transition-metal, high reaction temperatures, and stoichiometric chemical redox reagents. This approach was characterized by exceedingly mild conditions, ample substrate scope, and a commercially available catalyst. Gram-scale reactions and a telescoped synthesis route reflected the unique potential in the green synthesis of important S-heterocycles.