Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity. We hypothesized that small molecule targeted protein degradation (TPD) might result in differentiated pharmacology due to the loss of scaffolding functions. Here, we report the design and characterization of a potent CDK7 degrader that is comprised of an ATP-competitive CDK7 binder linked to a CRL2VHL recruiter. JWZ-5-13 effectively degrades CDK7 in multiple cancer cells and leads to a potent inhibition of cell proliferation. Additionally, compound JWZ-5-13 displayed bioavailability in a pharmacokinetic study conducted in mice. Therefore, JWZ-5-13 is a useful chemical probe to investigate the pharmacological consequences of CDK7 degradation.

As a toxic Volatile Organic Pollutant (TVOC), formaldehyde has a toxic effect on microorganisms, consequently inhibiting the biochemical process of formaldehyde wastewater treatment. Therefore, the selective degradation of formaldehyde is of great significance in achieving high-efficiency and low-cost formaldehyde wastewater treatment. This study constructed a heterogeneous Fe-ZSM-5/H2O2 Fenton system f or the selective degradation of target compounds. By immobilizing Fe3+ onto the surface of a ZSM-5 molecular sieve, Fe-ZSM-5 was prepared successfully. XRD, BET and FT-IR spectral studies showed that Fe-ZSM-5 was mainly composed of micropores. The influences of different variables on formaldehyde-selective heterogeneous Fenton degradation performance were studied. The 93.7% formaldehyde degradation and 98.2% selectivity of formaldehyde compared with glucose were demonstrated in the optimized Fenton system after 360 min. Notably, the resultant selective Fenton oxidation system had a wide range of pH suitability, from 3.0 to 10.0. Also, the Fe-ZSM-5 was used in five consecutive cycles without a significant drop in formaldehyde degradation efficiency. The use of reactive oxygen species scavengers indicated that the hydroxyl radical was the primary active species responsible for degrading formaldehyde. Furthermore, great degradation performance was acquired with high concentrations of formaldehyde for this system, and the degradation efficiency was more than 95.0%.

Photothermolysis is the process that converts radiation energy into thermal energy, which results in the destruction of surrounding tissues or cells through thermal diffusion. Laser therapy that is based on photothermolysis has been a widely used treatment for various skin diseases such as skin cancers and port-wine stains. It offers several benefits such as non-invasiveness and selective treatment. However, the use of light, e.g., laser, for safe and effective photothermolysis becomes challenging due to the limited penetration of light into skin tissue as well as the presence of melanin, which absorbs this light. To solve the current issues, we propose an optical microneedle-lens array (OMLA) coated with gold in this work to directly deliver light to targeted skin layers without being absorbed by surrounding tissues as well as melanin, which results in the improvement of the efficiency of photothermal therapy. We developed a novel fabrication method, frame-guided micromolding, to prepare the OMLA by assembling two negative molds with simultaneous alignment. In addition, evaluations of the optical and heat transfer characteristics of the OMLA were performed. We expect our developed OMLA to play a crucial role in realizing more effective laser therapy by allowing the precise delivery of photons to the target area.

Hemicellulose can be selectively removed by acid pretreatment. In this study, selective removal of hemicellulose was achieved using dilute sulfuric acid assisted by aluminum sulfate pretreatment. The optimal pretreatment conditions were 160 °C, 1.5 wt% aluminum sulfate, 0.7 wt% dilute sulfuric acid, and 40 min. A component analysis showed that the removal rate of hemicellulose and lignin reached 98.05% and 9.01%, respectively, which indicated that hemicellulose was removed with high selectivity by dilute sulfuric acid assisted by aluminum sulfate pretreatment. Structural characterizations (SEM, FTIR, BET, TGA, and XRD) showed that pretreatment changed the roughness, crystallinity, pore size, and functional groups of corn straw, which was beneficial to improve the efficiency of enzymatic hydrolysis. This study provides a new approach for the high-selectivity separation of hemicellulose, thereby offering novel insights for its subsequent high-value utilization.

BACKGROUND: Practicing and assessment of selective caries removal techniques in dental students remain challenges in many dental schools. The aim of this study was to utilize a 3D assessment technique, within a designated acceptable range of deviation, to evaluate the tendency of dental students in performing selective caries removal (SCR). The correlation between 3D assessment results and the conventional rubric rated by an instructor was also determined.
METHODS: Fifth-year dental students (n = 61) performed the SCR task on 3D-printed teeth containing simulated deep caries lesions in occlusal and proximal surfaces. One instructor assessed the results using a conventional analytic rubric. The excavated teeth were additionally evaluated using 3D analysis software with the designated acceptable range of deviations (± 0.5 mm) from the standard cavities. The average root mean square (RMS) value, representing the deviation between student-prepared cavities and the predefined standard cavities, was recorded. A tendency towards over-excavation was defined for RMS values > 0.5 mm, and towards under-excavation for RMS values < 0.5 mm.
RESULTS: The mean (min-max) of RMS was 0.27 (0.18-0.40) for occlusal and 0.29 (0.20-0.57)for proximal cavities. A tendency of dental students toward over-excavation was observed in both occlusal (74%) and proximal cavities (87%). There was a moderate negative correlation between the RMS values and the traditional rubric scores for both occlusal (R2 = 0.148, P = 0.002) and proximal cavities (R2 = 0.107, P = 0.010).
CONCLUSIONS: The 3D evaluation technique effectively revealed specific tendencies in dental students\' caries removal skills. The integration of computerized assessments with traditional methods could potentially assist the instructors in delivering more objective and specific feedback to students. Further research is encouraged to investigate the impact of this assessment technique on improving student performance in selective caries removal skills.

BACKGROUND: Gastric variceal hemorrhage is one of the primary manifestations of left-sided portal hypertension (LSPH). The hemorrhage is fatal and requires safe and effective interventions.
OBJECTIVE: To evaluate the clinical safety and efficacy of modified endoscopic ultrasound (EUS)-guided selective N-butyl-2-cyanoacrylate (NBC) injections for gastric variceal hemorrhage in LSPH.
METHODS: A retrospective observational study of patients with LSPH-induced gastric variceal hemorrhage was conducted. Preoperative EUS evaluations were performed. Enrolled patients were divided into modified and conventional groups according to the NBC injection technique. The final selection of NBC injection technique depended on the patients\' preferences and clinical status. The technical and clinical success rates, operation time, NBC doses, perioperative complications, postoperative hospital stay, and recurrent bleeding rates were analyzed, respectively.
RESULTS: A total of 27 patients were enrolled. No statistically significant differences were observed between the two groups regarding baseline characteristics. In comparison to patients in the conventional group, patients in the modified group demonstrated significantly reduced NBC doses (2.0 ± 0.6 mL vs 3.1 ± 1.0 mL; P = 0.004) and increased endoscopic operation time (71.9 ± 11.9 min vs 22.5 ± 6.7 min; P < 0.001). Meanwhile, the two groups had no significant difference in the technical and clinical success rates, perioperative complications, postoperative hospital stay, and recurrent bleeding rates.
CONCLUSIONS: Modified EUS-guided selective NBC injections demonstrated safety and efficacy for LSPH-induced gastric variceal hemorrhage, with advantages of reduced injection dose and no radiation risk. Drawbacks were time consumption and technical challenge.

Our study presents laser-assisted methods to produce conductive graphene layers on the polymer surface. Specimens were treated using two different lasers at ambient and nitrogen atmospheres. A solid-state picosecond laser generating 355 nm, 532 nm, or 1064 nm wavelengths and a CO2 laser generating mid-infrared 10.6 µm wavelength radiation operating in a pulsed regime were used in experiments. Sheet resistance measurements and microscopic analysis of treated sample surfaces were made. The chemical structure of laser-treated surfaces was investigated using Raman spectroscopy, and it showed the formation of high-quality few-layer graphene structures on the PI surface. The intensity ratios I(2D)/I(G) and I(D)/I(G) of samples treated with 1064 nm wavelength in nitrogen atmosphere were 0.81 and 0.46, respectively. After laser treatment, a conductive laser-induced graphene layer with a sheet resistance as low as 5 Ω was formed. Further, copper layers with a thickness of 3-10 µm were deposited on laser-formed graphene using a galvanic plating. The techniques of forming a conductive graphene layer on a polymer surface have a great perspective in many fields, especially in advanced electronic applications to fabricate copper tracks on 3D materials.

Helicobacter pylori is the primary cause of 78% of gastric cancer cases, providing an opportunity to prevent cancer by controlling a single bacterial pathogen within the complex gastric microbiota. We developed highly selective antimicrobial agents against H. pylori by fusing an H. pylori-binding guide peptide (MM1) to broad-spectrum antimicrobial peptides. The common dairy probiotic Lactococcus lactis was then engineered to secrete these guided antimicrobial peptides (gAMPs). When co-cultured in vitro with H. pylori, the gAMP probiotics lost no toxicity compared to unguided AMP probiotics against the target, H. pylori, while losing >90% of their toxicity against two tested off-target bacteria. To test binding to H. pylori, the MM1 guide was fused to green fluorescent protein (GFP), resulting in enhanced binding compared to unguided GFP as measured by flow cytometry. In contrast, MM1-GFP showed no increased binding over GFP against five different off-target bacteria. These highly selective gAMP probiotics were then tested by oral gavage in mice infected with H. pylori. As a therapy, the probiotics outperformed antibiotic treatment, effectively eliminating H. pylori in just 5 days, and also protected mice from challenge infection as a prophylactic. As expected, the gAMP probiotics were as toxic against H. pylori as the unguided AMP probiotics. However, a strong rebound in gastric species diversity was found with both the selective gAMP probiotics and the non-selective AMP probiotics. Eliminating the extreme microbial dysbiosis caused by H. pylori appeared to be the major factor in diversity recovery. IMPORTANCE Alternatives to antibiotics in the control of Helicobacter pylori and the prevention of gastric cancer are needed. The high prevalence of H. pylori in the human population, the induction of microbial dysbiosis by antibiotics, and increasing antibiotic resistance call for a more sustainable approach. By selectively eliminating the pathogen and retaining the commensal community, H. pylori control may be achieved without adverse health outcomes. Antibiotics are typically used as a therapeutic post-infection, but a more targeted, less disruptive approach could be used as a long-term prophylactic against H. pylori or, by extension, against other gastrointestinal pathogens. Furthermore, the modular nature of the guided antimicrobial peptide (gAMP) technology allows for the substitution of different guides for different pathogens and the use of a cocktail of gAMPs to avoid the development of pathogen resistance.

Two-thirds of survivors typically disclose their experience to informal supports (e.g., friends, family, partners) at some point following sexual assault, but little in-depth research has addressed specific aspects of disclosure. In the current study, a diverse sample of 45 sexual assault survivors and their informal support providers (SP; e.g., family, friends, romantic partners) were interviewed separately about experiences of disclosure, social reactions, and help-seeking following the assault. Narrative data on the overarching thematic category of selective disclosure were analyzed using thematic analysis methods. Several subthemes emerged specific to (a) the circumstances of disclosure (prompted or coerced), (b) withholding details (framing disclosures to avoid rape myths and blame, strategic use of language, protecting others by not disclosing or limiting details), and (c) sharing details (selecting who was told, selecting trusted others for disclosure, selective details told to specific people, sharing with strangers easier). Implications are drawn for future research on aspects of selective disclosure of sexual assault and clinical practice implications for supporting survivors and their informal support networks.

In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover \"off-label\" cases with significant benefits to the global healthcare economy.