Nerve bypass surgery for spinal cord reconstruction.

OBJECTIVE: Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves (ICNs) into the spinal cord. METHODS: Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of two pairs of ICNs from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. RESULTS: Six of the eight (75%) patients demonstrated motor and sensory improvements, based on the American Spinal Cord Injury Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid (CSF) leakage after surgery; however, only one patient complained of a headache. CONCLUSION: Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation.

Probing the CRL4DCAF12 interactions with MAGEA3 and CCT5 di-Glu C-terminal degrons.

Damaged DNA-binding protein-1 (DDB1)- and CUL4-associated factor 12 (DCAF12) serves as the substrate recognition component within the Cullin4-RING E3 ligase (CRL4) complex, capable of identifying C-terminal double-glutamic acid degrons to promote the degradation of specific substrates through the ubiquitin proteasome system. Melanoma-associated antigen 3 (MAGEA3) and T-complex protein 1 subunit epsilon (CCT5) proteins have been identified as cellular targets of DCAF12. To further characterize the interactions between DCAF12 and both MAGEA3 and CCT5, we developed a suite of biophysical and proximity-based cellular NanoBRET assays showing that the C-terminal degron peptides of both MAGEA3 and CCT5 form nanomolar affinity interactions with DCAF12 in vitro and in cells. Furthermore, we report here the 3.17 Šcryo-EM structure of DDB1-DCAF12-MAGEA3 complex revealing the key DCAF12 residues responsible for C-terminal degron recognition and binding. Our study provides new insights and tools to enable the discovery of small molecule handles targeting the WD40-repeat domain of DCAF12 for future proteolysis targeting chimera design and development.

Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies.

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae. These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases.

Opioid-free anesthesia: a practical guide for teaching and implementation.

Opioid-free anesthesia (OFA) represents an innovative approach that prioritizes patient safety, reduces the risks associated with opioid use, and seeks to enhance recovery. Few descriptions regarding the practical and implementation aspects exist. This review serves as a practical guide on OFA teaching and application. We briefly discuss the historical use of opioids in anesthesia, side effects and their consequences. We discuss pedagogical avenues and challenges, as well as implementation of OFA in less experienced settings. Opioid use in anesthesia originally coexisted with OFA. During the last decades, the advent of multimodal analgesia has resulted in decreased opioid dosages both before and after surgery. Recently, OFA increased in popularity, supported by meta-analyses, due to reduced nausea and vomiting, with a potential, even if limited, impact on pain. OFA, as part of rational prescribing, may contribute to a more patient-centered approach. Different strategies for OFA implementation coexist. Educational aspects, leadership, guidelines, local guidance, and training are all important. We propose a framework for OFA implementation with concrete options, including patient preparation, choice of OFA pharmacological agents (according to type of surgery and patient), and postoperative care. Whilst opioids still have an important place in pain management, they have brought harms that we cannot ignore. Evidence for using opioid-sparing and OFA techniques continues to emerge and there is a need to personalize more approaches. In this review, we provide evidence-based, relatively simple methods that can be used in implementing and delivering OFA.

Clinical characteristics and prognostic impact of direct distant organ metastasis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer worldwide, and distant metastasis is frequently noted at diagnosis or follow-up. Notably, some patients with CRC can present with distant organ metastasis without any nodal involvement, which was defined as direct distant organ metastasis (DDOM). In this study, we evaluated the prognostic significance of DDOM for patients with CRC. METHODS: This study included 325 patients who had undergone primary colorectal cancer resection between August 2008 and December 2021. The patients with and without DDOM were compared (Kaplan-Meier analysis) in terms of overall survival (OS) and time to recurrence. Furthermore, the patients' clinicopathological risk factors and protective factors were analyzed (multivariate Cox proportional hazards model). RESULTS: Of the 325 patients, 65 (20%) had DDOM (Direct+ group) and 260 (80%) did not (Direct- group). The Kaplan-Meier analysis revealed that OS was significantly better in the Direct+ group than in the Direct- group (p < 0.01). A subgroup analysis by CRC stage was performed; for the patients with non-stage-IV CRC, the rate of OS was significantly higher in the Direct+ group than in the Direct- group (p = 0.02). However, DDOM did not affect the OS of the patients with stage IV CRC. The multivariate analysis indicated DDOM, left colon tumor location, and postoperative adjuvant chemotherapy were significant protective factors for disease-related mortality in the patients with non-stage-IV CRC; by contrast, body mass index, curative resection, and postoperative adjuvant chemotherapy were identified to be significant protective factors in the patients with stage IV CRC. CONCLUSIONS: DDOM appears to be significantly associated with improved OS in patients with non-stage-IV CRC but not in those with stage IV CRC. Furthermore, the time to cancer recurrence may not vary significantly between patients with DDOM and those without it.

Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience.

Cardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.

Induced protein degradation for therapeutics: past, present, and future.

The concept of induced protein degradation by small molecules has emerged as a promising therapeutic strategy that is particularly effective in targeting proteins previously considered "undruggable." Thalidomide analogs, employed in the treatment of multiple myeloma, stand as prime examples. These compounds serve as molecular glues, redirecting the CRBN E3 ubiquitin ligase to degrade myeloma-dependency factors, IKZF1 and IKZF3. The clinical success of thalidomide analogs demonstrates the therapeutic potential of induced protein degradation. Beyond molecular glue degraders, several additional modalities to trigger protein degradation have been developed and are currently under clinical evaluation. These include heterobifunctional degraders, polymerization-induced degradation, ligand-dependent degradation of nuclear hormone receptors, disruption of protein interactions, and various other strategies. In this Review, we will provide a concise overview of various degradation modalities, their clinical applications, and potential future directions in the field of protein degradation.

A study of DNA transfers onto plastic packets placed in personal bags.

The ability to detect low level DNA brings with it the uncertainty of whether the detected DNA is a result of transfer. To address this uncertainty, a simulation study was conducted in which a mock illicit drug packet was placed into the personal bags of individuals. When the average transit time of the packets was increased from around 2 h to more than 14 h, the percentage of the DNA profiles recovered from the packets which could be attributed to the individuals increased greatly from 5.3% to 48.6%. We found that drug packers who were poor shedders could not be included as contributors to the DNA profiles from the drug packets at all and there was a higher chance that individuals other than themselves could be included as contributors to the DNA profile recovered from drug packets. We also found that it was equally likely that the drug packers who had direct contact with the drug packets and bag owners who did not, could be included as contributors to the DNA profiles recovered from the packets. The results in this study highlight the importance of taking into consideration the transit time of drug packet, the shedder status of the alleged packer and the history of an item, when evaluating DNA evidence in the context of illicit drug activities.

Epidermal Growth Factor Receptor Inhibitor Mobocertinib Resensitizes Multidrug-Resistant Cancer Cells by Attenuating the Human ATP-Binding Cassette Subfamily B Member 1 and Subfamily G Member 2.

ATP-binding cassette (ABC) transporters, notably ABCB1 (P-glycoprotein) and ABCG2, play a crucial role in the development of multidrug resistance (MDR) during the administration of chemotherapy for cancer patients. With a lack of approved treatments for addressing multidrug-resistant cancers, MDR remains a substantial challenge to the effective management of cancer. Rather than focusing on developing novel synthetic inhibitors, a promising approach to combat MDR involves repurposing approved therapeutic agents to enhance the sensitivity to cytotoxic antiproliferative drugs of multidrug-resistant cancer cells with high expression of ABCB1 or ABCG2. In this investigation, we observed a substantial reversal of MDR conferred by ABCB1 and ABCG2 in multidrug-resistant cancer cells through the use of mobocertinib, an approved third-generation inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Mobocertinib demonstrated the ability to hinder drug transport function without causing changes in protein expression. The interactions between mobocertinib and ABCB1, as well as ABCG2, were validated through ATPase assays. Furthermore, in silico docking simulations were utilized to substantiate the binding of mobocertinib within the drug-binding pockets of both ABCB1 and ABCG2. We conclude that further testing of mobocertinib in combination therapy is warranted for patients with tumors expressing elevated levels of the ABC drug transporters ABCB1 and ABCG2.

First 100 total hip arthroplasties performed by a young surgeon using the direct anterior approach: learning curve and complications.

INTRODUCTION: Most of the reported discussions about the learning curve for the direct anterior approach (DAA) in total hip arthroplasty (THA) have been by experienced surgeons. The study's aim was to describe the learning curve, short-term outcomes, complications, and adaptations to the DAA used in the first 100 THA cases experienced by a young surgeon who had received DAA training for trauma surgeries. MATERIALS AND METHODS: This retrospective study summarizes the first 100 consecutive cases experienced by a young surgeon who performed the unilateral DAA for THA between 2019 and 2021. Cumulative sum (CUSUM) analysis was performed to evaluate the learning curve on the basis of operative time and overall complications. The demographics data, short-term outcomes, and complications of the first 50 and second 50 cases were compared. RESULTS: The CUSUM curve declined after 49 and 55 cases, measured by operative time and overall complications, respectively. The median operative time (104 vs. 80 min) and intraoperative fluoroscopic time (38 vs. 12 s) increased significantly in the first 50 cases compared with the times in the second 50 cases. Complications tended to occur in the first 50 cases (12% vs. 6%), and the overall rate was 9%. Major complications all occurred in the first 50 cases, with a rate of 4%. Only one case, which involved a complicated periprosthetic fracture around the stem that extended to the tip, required the intervention of a senior surgeon. CONCLUSIONS: Even after receiving training on the DAA for trauma surgeries, the young surgeon experienced a steep learning curve and more complications in the first 50 cases. The DAA for THA is a technically demanding procedure and may require guidance from an experienced surgeon to manage unexpected complications.

Surgical reconstructions for adult brachial plexus injuries. Part II: Treatments for total arm type.

Brachial plexus injuries (BPI) contribute not only to physical dysfunction but also to socioeconomic aspects and psychological disability. Patients with total arm-type BPI will lose not only the shoulder and elbow function but also the hand function, making reconstruction particularly challenging. Reconstructive procedures commonly include nerve repair, grafting, neurotization (nerve transfer), tendon transfer and free functional muscle transfer (FFMT). Although it is difficult to achieve prehensile hand function, most of patients with total arm-type BPI can be treated with satisfied outcomes. In addition to surgical techniques, comprehensive rehabilitation is another important factor for successful outcomes, and efficient communication can help to boost patient morale and eliminate uncertainty.

Anophthalmic socket in retinoblastoma: Exploring complications and risk factors in a tertiary centre in Malaysia.

PURPOSE: To evaluate the complications of anophthalmic socket in retinoblastoma patients at a tertiary centre in Malaysia. DESIGN: Retrospective study. METHODS: Patients who underwent enucleation for retinoblastoma were reviewed from 2004-2020. Details were recorded, including demographics, diagnosis, surgical techniques, implant types, additional therapies, and complications. RESULTS: Of 250 patients with retinoblastoma managed over the period, the anophthalmic sockets of 160 eyes who underwent enucleation were analysed. The mean age at enucleation was 2.03 years (26 days to 9.18 years). The follow-up periods after enucleation range from 5 days to 16.83 years. Porous polyethylene (Medpor) implants were used in 135 patients (84.4%), as were Bioceramic in 9, glass balls in 7, acrylic in 7, dermis fat grafts in 1, and silicone implants (Aurosphere) in 1. The overall complications in our study were 28.8%. Complications seen in the study included implant exposure (12.5%), shallow inferior fornix (10.6%), granuloma formation (3.1%), discharge (2.5%), implant migration (1.9%), ptosis (0.6%), and orbital dystopia (0.6%). Implant exposure is solely found in Medpor, more common in those with donor sclera caps, and exposure times range from 28 days to 11.42 years. The suturing of the Tenon and conjunctiva in separate layers significantly reduced the rate of implant exposure. Six out of seven radiation patients had shallow inferior fornixes. CONCLUSIONS: Long-term post-enucleation complications were not uncommon. Luckily, most had good outcomes, with a few needing surgical intervention. Meticulous suturing technique on the Tenon and conjunctival layer is essential to prevent implant exposure.

The cross-race effect in automatic facial expression recognition violates measurement invariance.

Emotion has been a subject undergoing intensive research in psychology and cognitive neuroscience over several decades. Recently, more and more studies of emotion have adopted automatic rather than manual methods of facial emotion recognition to analyze images or videos of human faces. Compared to manual methods, these computer-vision-based, automatic methods can help objectively and rapidly analyze a large amount of data. These automatic methods have also been validated and believed to be accurate in their judgments. However, these automatic methods often rely on statistical learning models (e.g., deep neural networks), which are intrinsically inductive and thus suffer from problems of induction. Specifically, the models that were trained primarily on Western faces may not generalize well to accurately judge Eastern faces, which can then jeopardize the measurement invariance of emotions in cross-cultural studies. To demonstrate such a possibility, the present study carries out a cross-racial validation of two popular facial emotion recognition systems-FaceReader and DeepFace-using two Western and two Eastern face datasets. Although both systems could achieve overall high accuracies in the judgments of emotion category on the Western datasets, they performed relatively poorly on the Eastern datasets, especially in recognition of negative emotions. While these results caution the use of these automatic methods of emotion recognition on non-Western faces, the results also suggest that the measurements of happiness outputted by these automatic methods are accurate and invariant across races and hence can still be utilized for cross-cultural studies of positive psychology.

Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport.

The high expression of the ATP-binding cassette (ABC) drug transporter ABCG2 in cancer cells contributes to the emergence of multidrug resistance (MDR) in individuals afflicted with either solid tumors or blood cancers. MDR poses a major impediment in the realm of clinical cancer chemotherapy. Recently, substantial endeavors have been dedicated to identifying bioactive compounds isolated from nature capable of counteracting ABCG2-mediated MDR in cancer cells. Imperatorin, a natural coumarin derivative renowned for its diverse pharmacological properties, has not previously been explored for its impact on cancer drug resistance. This study investigates the chemosensitizing potential of imperatorin in ABCG2-overexpressing cancer cells. Experimental results reveal that at sub-toxic concentrations, imperatorin significantly antagonizes the activity of ABCG2 and reverses ABCG2-mediated MDR in a concentration-dependent manner. Furthermore, biochemical data and in silico analysis of imperatorin docking to the inward-open conformation of human ABCG2 indicate that imperatorin directly interacts with multiple residues situated within the transmembrane substrate-binding pocket of ABCG2. Taken together, these results furnish substantiation that imperatorin holds promise for further evaluation as a potent inhibitor of ABCG2, warranting exploration in combination drug therapy to enhance the effectiveness of therapeutic agents for patients afflicted with tumors that exhibit high levels of ABCG2.

Autologous anterior lens capsule flap and serum transplant in managing idiopathic and refractory full-thickness macular holes.

PURPOSE: To report the results of pars plana vitrectomy (PPV) with inner limiting membrane (ILM) peeling alongside phacoemulsification and intraocular lens (IOL) implantation with autologous anterior lens capsule flap (ALCF) and autologous serum transplantation (AST) into full-thickness macular holes (FTMH) and 14% perfluoropropane (C3F8) tamponade for idiopathic and refractory FTMHs. METHODS: Retrospective study involving eleven patients with idiopathic FMTHs and seven with refractory FMTHs after standard surgery with PPV, ILM peeling, and gas tamponade. All eyes underwent a 'combination procedure' of PPV with ILM peeling alongside phacoemulsification and IOL implantation with autologous ALCF and AST into the FTMH and 14% C3F8 tamponade. A face-down position for one week was recommended. RESULTS: The mean preoperative FMTH size was 558.95 ± 186.30 µm. Seven patients aged 64 ± 5 years had a refractory FMTH and eleven patients with a mean age of 63.72 ± 4.97 years had an idiopathic FMTH. The main BCVA improvement six months postoperatively was 0.3 ± 0.29 logMAR. Seventeen macular holes fully closed six months postoperatively, with one FTMH closure failure because of a retinal detachment. CONCLUSIONS: ALCF transplantation alongside AST may help to improve the closure rate and visual outcomes in both idiopathic and refractory FMTHs.

The Impact of Cefuroxime Susceptibility on Aeromonas Necrotizing Fasciitis Outcomes.

Despite aggressive antibiotic therapy and surgical debridement, Aeromonas necrotizing fasciitis (NF) can lead to high amputation and mortality rates. Our study compares the different antibiotic minimum inhibitory concentrations (MICs) via Epsilometer tests (E-tests) between non-survivors and survivors of Aeromonas NF of limbs. A prospective review of 16 patients with Aeromonas NF was conducted for 3.5 years in a tertiary coastal hospital. E-tests were conducted for 15 antimicrobial agents to determine the MIC value for Aeromonas species. These patients were divided into non-survival and survival groups. The clinical outcomes, demographics, comorbidities, presenting signs and symptoms, laboratory findings, and microbiological results between the two periods were compared. A total of four patients died, whereas 12 survived, resulting in a 25% mortality rate. A higher proportion of bloodstream infections (100% vs. 41.7%; p = 0.042), monomicrobial infections (100% vs. 33.3%; p = 0.021), shock (100% vs. 33.3%; p = 0.021), serous bullae (50% vs. 0%; p = 0.009), liver cirrhosis (100% vs. 25%; p = 0.009), chronic kidney disease (100% vs. 33.3%; p = 0.021), lower susceptibility to cefuroxime (25% vs. 83.3%; p = 0.028), and ineffective antibiotic prescriptions (75% vs. 16.7%; p = 0.029) was observed in non-survivors. Aeromonas NF is an extremely rare skin and soft-tissue infection that is associated with high mortality, bacteremia, antibiotic resistance, and polymicrobial infection. Therefore, antibiotic regimen selection is rendered very challenging. To improve clinical outcomes and irrational antimicrobial usage, experienced microbiologists can help physicians identify specific pathogens and test MIC.

Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning.

WD40 repeat-containing protein 91 (WDR91) regulates early-to-late endosome conversion and plays vital roles in endosome fusion, recycling, and transport. WDR91 was recently identified as a potential host factor for viral infection. We employed DNA-encoded chemical library (DEL) selection against the WDR domain of WDR91, followed by machine learning to predict ligands from the synthetically accessible Enamine REAL database. Screening of predicted compounds identified a WDR91 selective compound 1, with a KD of 6 ± 2 µM by surface plasmon resonance. The co-crystal structure confirmed the binding of 1 to the WDR91 side pocket, in proximity to cysteine 487, which led to the discovery of covalent analogues 18 and 19. The covalent adduct formation for 18 and 19 was confirmed by intact mass liquid chromatography-mass spectrometry. The discovery of 1, 18, and 19, accompanying structure-activity relationship, and the co-crystal structures provide valuable insights for designing potent and selective chemical tools against WDR91 to evaluate its therapeutic potential.

Facile Blending Strategy for Boosting the Conjugated Polymer Semiconductor Transistor's Mobility.

The optimization of field-effect mobility in polymer field-effect transistors (FETs) is a critical parameter for advancing organic electronics. Today, many challenges still persist in understanding the roles of the design and processing of semiconducting polymers toward electronic performance. To address this, a facile approach to solution processing using blends of PDPP-TVT and PTPA-3CN is developed, resulting in a 3.5-fold increase in hole mobility and retained stability in electrical performance over 3 cm2 V-1 s-1 after 20 weeks. The amorphous D-A conjugated structure and strong intramolecular polarity of PTPA-3CN are identified as major contributors to the observed improvements in mobility. Additionally, the composite analysis by X-ray photoelectron spectroscopy (XPS) and the flash differential scanning calorimetry (DSC) technique showed a uniform distribution and was well mixed in binary polymer systems. This mobility enhancement technique has also been successfully applied to other polymer semiconductor systems, offering a new design strategy for blending-type organic transistor systems. This blending methodology holds great promise for the practical applications of OFETs.

Exploration of the Tunability of BRD4 Degradation by DCAF16 Trans-labelling Covalent Glues.

Small molecules that can induce protein degradation by inducing proximity between a desired target and an E3 ligase have the potential to greatly expand the number of proteins that can be manipulated pharmacologically. Current strategies for targeted protein degradation are mostly limited in their target scope to proteins with preexisting ligands. Alternate modalities such as molecular glues, as exemplified by the glutarimide class of ligands for the CUL4CRBN ligase, have been mostly discovered serendipitously. We recently reported a trans-labelling covalent glue mechanism which we named 'Template-assisted covalent modification', where an electrophile decorated small molecule binder of BRD4 was effectively delivered to a cysteine residue on an E3 ligase DCAF16 as a consequence of a BRD4-DCAF16 protein-protein interaction. Herein, we report our medicinal chemistry efforts to evaluate how various electrophilic modifications to the BRD4 binder, JQ1, affect DCAF16 trans-labeling and subsequent BRD4 degradation efficiency. We discovered a decent correlation between the ability of the electrophilic small molecule to induce ternary complex formation between BRD4 and DCAF16 with its ability to induce BRD4 degradation. Moreover, we show that a more solvent-exposed warhead presentation is optimal for DCAF16 recruitment and subsequent BRD4 degradation. Unlike the sensitivity of CUL4CRBN glue degraders to chemical modifications, the diversity of covalent attachments in this class of BRD4 glue degraders suggests a high tolerance and tunability for the BRD4-DCAF16 interaction. This offers a potential new avenue for a rational design of covalent glue degraders by introducing covalent warheads to known binders.