In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

Positional information plays a crucial role in embryonic pattern formation, yet its role in tooth development remains unexplored. In this study, we investigated the regional specification of lingual and buccal dental mesenchyme during tooth development. Tooth germs at the cap stage were dissected from mouse mandibles, and their lingual and buccal mesenchymal regions were separated for bulk RNA sequencing. Gene ontology analysis revealed that odontogenesis, pattern specification, and proliferation-related genes were enriched in the lingual mesenchyme, whereas stem cell development, mesenchymal differentiation, neural crest differentiation, and regeneration-related genes were predominant in the buccal mesenchyme. Reaggregation experiments using Wnt1^creERT/+; R26R^tdT/+ and WT mouse models demonstrated that lingual mesenchyme contributes to tooth formation, while buccal mesenchyme primarily supports surrounding tissues. Furthermore, only the lingual part of tooth germs exhibited odontogenic potential when cultured in vitro and transplanted under the kidney capsule. Bulk RNA transcriptomic analysis further validated the regional specification of the lingual and buccal mesenchyme. These findings provide novel insights into the molecular basis of positional information in tooth development and pattern formation.
Animals ; Mice ; Odontogenesis/genetics* ; Tooth Germ/cytology* ; Mesoderm/cytology* ; Cell Differentiation ; Mesenchymal Stem Cells ; Tooth/embryology*

Chronic recurrent sialadenitis is characterized by repeated inflammation of the salivary glands, leading to ductal structural abnormalities and salivary stasis, often resulting in megaducts. This study evaluates the efficacy of ultrasonography as a diagnostic and follow-up tool for the management of chronic recurrent sialadenitis. Three patients underwent sialendoscopy, which involved ductal dilation, removal of mucous plugs, and steroid administration. Ultrasonography was used postoperatively to monitor changes in ductal structure, including megaduct size, and to assess clinical outcomes.All three cases showed marked improvement in clinical symptoms after treatment. Ultrasonography demonstrated a reduction in megaduct size and provided real-time visualization of ductal and glandular changes. Compared to traditional imaging methods such as magnetic resonance imaging or sialography, ultrasonography offered a practical and safe option for follow-up assessment. This study highlights the utility of ultrasonography as an accessible, non-invasive, and effective tool for evaluating treatment outcomes in chronic recurrent sialadenitis. By offering detailed visualization of ductal changes and facilitating longitudinal follow-up, ultrasonography can optimize the management of this condition.

The population attributable fraction (PAF) indicates the proportion of disease cases in a given population that can be attributed to a specific factor, assuming a causal relationship. In other words, it quantifies the extent to which that factor contributes to disease occurrence. PAF calculation methods have been applied to studies factors and several, studies have reported PAFs for dietary contributors to overall or specific cancer risks. Our team has conducted several PAF studies and presents findings on the contributions of dietary factors to cancer risk in the Korean population.Current Concepts: For colorectal cancer, the PAF of dietary factors is 34.9%, with insufficient whole grain intake contributing the largest share (16.6%). For gastric cancer, dietary factors have a PAF of 18.6%, with excessive intake of salted vegetables contributing the most (16.0%). Notably, the PAFs for inadequate whole grain and milk consumption were higher than those reported in previous studies, while the PAFs for other dietary factors fell within the expected range. These findings emphasize the need to prioritize interventions that effectively reduce the diet-attributable cancer burden.Discussion and Conclusion: Country-specific PAF estimates are crucial for developing effective cancer prevention strategies tailored to the Korean population. To better apply dietary PAF estimates, future studies should (1) integrate data from existing and ongoing cohort studies to determine Korea-specific relative risks, (2) estimate dietary prevalence using assessment tools that capture long-term dietary habits, and (3) establish optimal intake levels specific to the Korean context.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Purpose: To report a case of infectious keratitis and endophthalmitis caused by two types of antibiotic-resistant bacteria.Case summary: A 62-year-old female patient presented to our clinic with left ocular pain for 2 weeks and was diagnosed with herpetic keratitis and anterior uveitis. At the initial presentation, slit lamp biomicroscopy revealed round stromal infiltration and edema in the paracentral part of the cornea, a 2 × 2-mm epithelial defect, and hypopyon. Ocular ultrasonography showed vitreous opacities. She was empirically treated with topical 0.5% moxifloxacin, 2% tobramycin, and 5% ceftazidime administered hourly. Intravitreal vancomycin/ceftazidime administration was performed on days 2 and 7 following treatment. Corneal culture revealed extended-spectrum β-lactamase-producing Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus on day 4 after treatment. Consequently, 2% tobramycin was replaced with 1% vancomycin. The corneal lesion gradually improved and healed completely with a residual corneal opacity at 4 weeks after treatment. Conclusions Polymicrobial bacterial keratitis caused by antibiotic-resistant bacteria represents a treatment challenge. Therefore, culture is essential to obtain microbiological evidence and guide appropriate antibiotic selection.

Objective: The Daegu region experienced the first wave of the pandemic at the beginning of the coronavirus disease 2019 (COVID-19) outbreak in Korea. Other non-COVID-19-related treatments during a community outbreak, such as cardiovascular diseases, were expected to impact emergency departments. In acute myocardial infarctions, time is an important factor affecting the patient outcome. This study examined how community COVID-19 outbreak affected STsegment elevated myocardial infarction (STEMI) care in emergency departments. Methods: A retrospective analysis was performed on patients visiting five emergency departments in the Daegu area who were diagnosed with STEMI from February 18 to April 17 each year from 2018 to 2020. The demographic characteristics, prehospital variables, in-hospital time variables, and treatment results were collected. The cases were divided into the pre-COVID period and the COVID period for comparison. Results: The study included 254 patients (194 pre-COVID, 60 during COVID). The symptom-to-door time did not differ. Although the door-to-first doctor time was shortened (4 min vs. 2 min, P=0.01), the rate of coronary angiogram along with the door-to-angiogram time and the door-to-balloon time did not change. The length of stay in the emergency department was delayed during COVID-19 (median, 136 min vs. 404 min; P<0.01). The in-hospital length of stay and mortality were similar in both groups. Conclusion The time to treat STEMI was not delayed significantly during the first wave of the COVID-19 outbreak in the Daegu area compared with the pre-pandemic period. Mortality did not change. The length of stay was elongated significantly in the emergency department but not in the hospital.

Objective: It has been 1 year since the start of the worldwide coronavirus disease-19 (COVID-19) pandemic. This study analyzed the indirect effects of COVID-19 on treating patients with non-infectious diseases by comparing the incidence of complicated appendicitis before and after the pandemic. Methods: The target group included patients aged at least 16 years diagnosed with acute appendicitis between February 23 and July 31, 2020. Patients diagnosed during the same period in 2019 were selected as the control group. The differences in the incidence of complicated appendicitis before and after COVID-19 were investigated, and the association with various variables was analyzed using the odds ratios and 95% confidence intervals (CIs). Results: The study included 120 subjects in 2019 (pre-COVID group) and 119 cases in 2020 (post-COVID group). The pre-COVID group included 25 cases (20.8%) of complicated appendicitis, while the post-COVID group included 48 cases (40.3%). The median time from symptom onset to visit (pre-hospital time) increased from 15 to 22 hours, and the median time from the visit to surgery (in-hospital time) increased from 7 to 11 hours. Multivariate regression analysis of the three variables revealed odds ratios (95% CIs) of pre-hospital time, erythrocyte sedimentation rate, and inclusion in the post-COVID group of 1.02 (1.01-1.02), 2.07 (1.11-3.86), and 2.15 (1.12-4.11), respectively. Conclusion The incidence of complicated appendicitis increased after the COVID-19 pandemic. Therefore, a healthcare system that can minimize the delay in treating non-infectious emergency patients is needed.