Enhanced efficacy of glycoengineered rice cell-produced trastuzumab.

For several decades, a plant-based expression system has been proposed as an alternative platform for the production of biopharmaceuticals including therapeutic monoclonal antibodies (mAbs), but the immunogenicity concerns associated with plant-specific N-glycans attached in plant-based biopharmaceuticals has not been completely solved. To eliminate all plant-specific N-glycan structure, eight genes involved in plant-specific N-glycosylation were mutated in rice (Oryza sativa) using the CRISPR/Cas9 system. The glycoengineered cell lines, PhytoRice®, contained a predominant GnGn (G0) glycoform. The gene for codon-optimized trastuzumab (TMab) was then introduced into PhytoRice® through Agrobacterium co-cultivation. Selected cell lines were suspension cultured, and TMab secreted from cells was purified from the cultured media. The amino acid sequence of the TMab produced by PhytoRice® (P-TMab) was identical to that of TMab. The inhibitory effect of P-TMab on the proliferation of the BT-474 cancer cell line was significantly enhanced at concentrations above 1 µg/mL (****P < 0.0001). P-TMab bound to a FcγRIIIa variant, FcγRIIIa-F158, more than 2.7 times more effectively than TMab. The ADCC efficacy of P-TMab against Jurkat cells was 2.6 times higher than that of TMab in an in vitro ADCC assay. Furthermore, P-TMab demonstrated efficient tumour uptake with less liver uptake compared to TMab in a xenograft assay using the BT-474 mouse model. These results suggest that the glycoengineered PhytoRice® could be an alternative platform for mAb production compared to current CHO cells, and P-TMab has a novel and enhanced efficacy compared to TMab.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

PIP-Seq identifies novel heterogeneous lung innate lymphocyte population activation after combustion product exposure.

Innate lymphoid cells (ILCs) are a heterogeneous population that play diverse roles in airway inflammation after exposure to allergens and infections. However, how ILCs respond after exposure to environmental toxins is not well understood. Here we show a novel method for studying the heterogeneity of rare lung ILC populations by magnetic enrichment for lung ILCs followed by particle-templated instant partition sequencing (PIP-seq). Using this method, we were able to identify novel group 1 and group 2 ILC subsets that exist after exposure to both fungal allergen and burn pit-related constituents (BPC) that include dioxin, aromatic hydrocarbon, and particulate matter. Toxin exposure in combination with fungal allergen induced activation of specific ILC1/NK and ILC2 populations as well as promoted neutrophilic lung inflammation. Oxidative stress pathways and downregulation of specific ribosomal protein genes ( Rpl41 and Rps19 ) implicated in anti-inflammatory responses were present after BPC exposure. Increased IFNγ expression and other pro-neutrophilic mediator transcripts were increased in BPC-stimulated lung innate lymphoid cells. Further, the addition of BPC induced Hspa8 (encodes HSC70) and aryl hydrocarbon transcription factor activity across multiple lung ILC subsets. Overall, using an airway disease model that develops after occupational and environmental exposures, we demonstrate an effective method to better understand heterogenous ILC subset activation.

Corrigendum: Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

[This corrects the article DOI: 10.3389/fonc.2024.1368926.].

OTUD6A orchestrates complex modulation of TEAD4-mediated transcriptional programs.

TEAD transcription factors play a central role in the Hippo signaling pathway. In this study, we focused on transcriptional enhancer factor TEF-3 (TEAD4), exploring its regulation by the deubiquitinase OTU domain-containing protein 6A (OTUD6A). We identified OTUD6A as a TEAD4-interacting deubiquitinase, positively influencing TEAD-driven transcription without altering TEAD4 stability. Structural analyses revealed specific interaction domains: the N-terminal domain of OTUD6A and the YAP-binding domain of TEAD4. Functional assays demonstrated the positive impact of OTUD6A on the transcription of YAP-TEAD target genes. Despite no impact on TEAD4 nuclear localization, OTUD6A selectively modulated nuclear interactions, enhancing YAP-TEAD4 complex formation while suppressing VGLL4 (transcription cofactor vestigial-like protein 4)-TEAD4 interaction. Critically, OTUD6A facilitated YAP-TEAD4 complex binding to target gene promoters. Our study unveils the regulatory landscape of OTUD6A on TEAD4, providing insights into diseases regulated by YAP-TEAD complexes.

A Preliminary Evaluation of the Diagnostic Performance of a Smartphone-Based Machine Learning-Assisted System for Evaluation of Clinical Activity Score in Digital Images of Thyroid-Associated Orbitopathy.

Background: We previously developed a machine learning (ML)-assisted system for predicting the clinical activity score (CAS) in thyroid-associated orbitopathy (TAO) using digital facial images taken by a digital single-lens reflex camera in a studio setting. In this study, we aimed to apply this system to smartphones and detect active TAO (CAS ≥3) using facial images captured by smartphone cameras. We evaluated the performance of our system on various smartphone models and compared it with the performance of ophthalmologists with varying clinical experience. Methods: We applied the preexisting ML architecture to classify photos taken with smartphones (Galaxy S21 Ultra, iPhone 12 pro, iPhone 11, iPhone SE 2020, Galaxy M20, and Galaxy A21S). The performance was evaluated with smartphone-captured images from 100 patients with TAO. Three ophthalmology residents, three general ophthalmologists with <5 years of clinical experience, and three oculoplastic specialists independently interpreted the same set of images taken under a studio environment and compared their results with those generated by the smartphone-based ML-assisted system. Reference CAS was determined by a consensus of three oculoplastic specialists. Results: Active TAO (CAS ≥3) was identified in 28 patients. Smartphone model used in capturing facial images influenced active TAO detection performance (F1 score 0.59-0.72). The smartphone-based system showed 74.5% sensitivity, 84.8% specificity, and F1 score 0.70 on top three smartphones. On images from all six smartphones, average sensitivity, specificity, and F1 score were 71.4%, 81.6%, and 0.66, respectively. Ophthalmology residents' values were 69.1%, 55.1%, and 0.46. General ophthalmologists' values were 61.9%, 79.6%, and 0.55. Oculoplastic specialists' values were 73.8%, 90.7%, and 0.75. This smartphone-based ML-assisted system predicted CAS within 1 point of reference CAS in 90.7% using facial images from smartphones. Conclusions: Our smartphone-based ML-assisted system shows reasonable accuracy in detecting active TAO, comparable with oculoplastic specialists and outperforming residents and general ophthalmologists. It may enable reliable self-monitoring for disease activity, but confirmatory research is needed for clinical application.

Radical prostatectomy versus radiotherapy as local therapy for primary tumors in patients with oligometastatic prostate cancer.

Introduction: We compared radical prostatectomy (RP) and radiotherapy (RT) as local therapies for primary tumors and examined their associations with survival outcomes and urinary tract complications in patients with oligometastatic prostate cancer (omPC). Methods: We evaluated the data of 85 patients diagnosed with omPC who underwent local therapy for primary tumors between January 2008 and December 2018. Of the 85 patients, 31 underwent prostate RT, while 54 underwent RP. Oligometastatic disease was defined as the presence of fewer than five metastatic lesions without visceral metastasis. Urinary tract complications, progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) were evaluated using the Kaplan-Meier method and Cox regression analyses. Results: Patients treated with RT showed higher prostate-specific antigen levels. There was no significant difference in the 5-year PFS (52.5% vs. 37.9%, p=0.351), CSS (67.6% vs. 84.7%, p=0.473), or OS (63.6% vs. 73.8%, p=0.897) between the RT and RP groups. In the multivariate analyses, the type of local therapy was not associated with PFS (hazard ratio [HR]=1.334, p=0.356), CSS (HR=0.744, p=0.475), or OS (HR=0.953, p=0.897). Conclusion: Therefore, RP seems to be a possible treatment option for patients with omPC, exhibiting oncologic outcomes comparable to those with RT.

ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy.

Most patients diagnosed with clear cell renal cell carcinoma (ccRCC) are also detected with small and organ-confined tumors, and the majority of these are classified as clinical tumor stage 1a (cT1a). A considerable proportion of patients with cT1 RCC shows tumor upstaging to pathological stage 3a (pT3a), and these patients have worse oncological outcomes. The role of circulating tumor DNA (ctDNA) in RCC has been limited to monitoring treatment response and resistance. Therefore, the present study aimed to evaluate the potential of ctDNA in predicting pT3a upstaging in cT1a ccRCC. We sequenced plasma samples preoperatively collected from 48 patients who had undergone partial nephrectomy for cT1a ccRCC using data from a prospective cohort RCC. The ctDNA were profiled and compared with clinicopathological ccRCC features to predict pT3a upstaging. Associations between ctDNA, tumor complexity, and pT3a upstaging were evaluated. Tumor complexity was assessed using the anatomical classification system. Univariate analysis used chi-squared and Student's t-tests; multivariate analysis considered significant factors from univariate analyses. Of the 48 patients with cT1a ccRCC, 12 (25%) were upstaged to pT3a, with ctDNA detected in 10 (20.8%), predominantly in patients with renal sinus fat invasion (SFI; n = 8). Among the pT3a group, ctDNA was detected in 75%, contrasting with only 2.8% in patients with pT1a (1/36). Detection of ctDNA was the only significant preoperative predictor of pT3a upstaging, especially in SFI. This study is the first to suggest ctDNA as a preoperative predictor of pT3a RCC upstaging from cT1a based on preoperative radiological images.

Risks of Dementia After Treatment with an Anticholinergic, Beta-3 Agonist, or Combination of Both for an Overactive Bladder: A Korean National Cohort Study.

BACKGROUND AND OBJECTIVE: An overactive bladder (OAB) is primarily managed with behavioural therapy and using anticholinergics and beta-3 agonists. Reports have shown that the use of anticholinergics by OAB patients was associated with an increased risk of new-onset dementia compared with those using beta-3 agonists. This study compares the risks of dementia among patients with an OAB starting on a beta-3 agonist alone, an anticholinergic alone, or a combination treatment. METHODS: Using data from the Korean National Health Insurance Service database, we studied a nationwide population cohort comprising patients newly diagnosed with an OAB who initiated their OAB medications between 2015 and 2020. The treatment types were categorised as anticholinergics (oxybutynin, solifenacin, tolterodine, trospium, fesoterodine, flavoxate, and propiverine) alone, a beta-3 agonist (mirabegron) alone, and combination therapy (an anticholinergic plus the beta-3 agonist). To evaluate the impact of cumulative drug exposure, we quantified the cumulative exposure to solifenacin and mirabegron as cumulative defined daily doses (cDDDs) using proportional hazards regression analyses, adjusted for factors known to be associated with dementia. KEY FINDINGS AND LIMITATIONS: Among the study's 3 452 705 patients, 671 974 were new users of a beta-3 agonist alone (19.5%), 1 943 414 new users of anticholinergics alone (56.3%), and 837 317 receiving combination therapy (24.3%). The most common anticholinergic used both alone and as part of a combination treatment was solifenacin (42.9% and 56.3%, respectively). There was an increased risk of dementia between the users of an anticholinergic alone (adjusted hazard ratio [aHR] = 1.213; 95% confidence interval [CI], 1.195-1.232) and those taking a combination treatment (aHR = 1.345; 95% CI, 1.323-1.366) compared with the users of beta-3 agonists alone after the adjustment of covariates. However, the incidence of dementia was also significantly higher, with an increase in the cumulative dose of mirabegron (aHR = 1.062 [1.021-1.106] for 28-120 cDDDs and aHR = 1.044 [1.004-1.084)] for patients who received >121 cDDDs compared with those who received <27 cDDDs). A marked increased risk of dementia was associated with the use of solifenacin, tolterodine, fesoterodine, and propiverine, both separately and in combination with mirabegron. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this large Korean cohort, the use of anticholinergics with or without a beta-3 agonist increased the risk of new-onset dementia compared with the use of a beta-3 agonist alone. Given that the risk of dementia was most significantly elevated with combination treatments, care should be taken when considering combination treatment for OAB patients with risk factors for dementia. Furthermore, there could be a possible association between beta-3 agonists and dementia, although future studies are needed. PATIENT SUMMARY: This study investigated the risk of dementia induced by overactive bladder (OAB) treatment in a large Korean cohort. Two representative OAB treatment drugs, anticholinergics and beta-3 agonists, both increased the risk of new-onset dementia. Clinicians should be cautious in using OAB treatment drugs since no drugs could be concluded as safe.

PD-1 inhibitor plus oncolytic vaccinia virus is a safe and effective treatment option for metastatic renal cell carcinoma.

BACKGROUND: Although a combination of immune checkpoint inhibitors (ICIs) is recommended as the first line treatment option for metastatic renal cell carcinoma (mRCC), several immune-related adverse events (irAEs) occur, especially hepatitis. We explored the therapeutic benefits and safety profile of combining oncolytic vaccinia virus, JX-594, with a programmed cell death protein-1 (PD-1) inhibitor. METHODS: We used early-stage and advanced-stage orthotopic murine mRCC models developed by our group. PD-1 inhibitor monotherapy or a PD-1 inhibitor combined with either JX-594 or a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor were systemically injected through the peritoneum. An immunofluorescence analysis was performed to analyze the tumor immune microenvironment (TIME). irAEs were assessed in terms of hepatitis. RESULTS: In the early-stage mRCC model mice, the combination of JX-594 and a PD-1 inhibitor significantly decreased the primary tumor size and number of lung nodules, compared with the ICI combination, but the JX-594 and PD-1 inhibitor combination and ICI combination did not differ significantly in the advanced-stage mRCC model mice. The JX-594 and PD-1 inhibitor combination induced tumor-suppressing TIME changes in both the early- and advanced-stage mRCC models. Furthermore, mice treated with the ICI combination had significantly greater hepatic injuries than those treated with the JX-594 and PD-1 inhibitor combination which was evaluated in early-stage mRCC model. CONCLUSIONS: The JX-594 and PD-1 inhibitor combination effectively reduced primary tumors and the metastatic burden, similar to ICI combination therapy, through dynamic remodeling of the TIME. Furthermore, hepatitis was significantly decreased in the JX-594 and PD-1 inhibitor combination group, suggesting the potential benefit of that combination for reducing ICI-induced toxicity.

Role of Maximal Transurethral Resection Preceding Partial Cystectomy for Muscle-Invasive Bladder Cancer.

PURPOSE: We aimed to evaluate whether maximal transurethral resection (TUR) affects the oncological outcome of partial cystectomy (PC) performed in patients with muscle-invasive bladder cancer (MIBC), although radical cystectomy (RC) and trimodal therapy (TMT) are regarded as standard treatments for MIBC. METHODS: In this retrospective study, we evaluated the data of 98 patients who underwent PC due to MIBC between January 2006 and December 2018. Of the 98 patients, 71 underwent maximal TUR. We evaluated the recurrence-free survival (PFS), pelvic recurrence-free survival (pPFS), cancer-specific survival (CSS), and overall survival (OS) using the Kaplan-Meier method according to the maximal TUR status. Variables associated with survival were analyzed using Cox regression analyses. RESULTS: The 5-year PFS (42.5% vs. 20.3%, p = 0.008), pPFS (50.7% vs. 24.1%, p = 0.003), and CSS (74.0% vs. 51.0%, p = 0.016) were also higher in patients who underwent maximal TUR. The multivariable Cox regression analysis showed that maximal TUR was associated with PFS (hazard ratio [HR] = 0.500, p = 0.029), pPFS (HR = 0.353, p = 0.004), and CSS (HR = 0.416, p = 0.027). However, maximal TUR did not affect the OS (HR = 0.618, p = 0.132). CONCLUSION: PC resulted in acceptable oncological outcomes in patients with MIBC, while maximal TUR played an important role in improving the oncological outcomes. PC after maximal TUR can be suggested as a treatment option for MIBC patients who are unable to undergo RC and TMT.

Pharmaceutical and Immunological Evaluation of Cholera Toxin A1 Subunit as an Adjuvant of Hepatitis B Vaccine Microneedles.

PURPOSE: For successful delivery of a solid vaccine formulation into the skin using microneedles, the solubility of an adjuvant should be considered because the decrease in the dissolution rate by the addition of adjuvant decreases the delivery efficiency of the vaccine. METHODS: In this study, cholera toxin A subunit 1 (CTA1) was examined as an adjuvant to Hepatitis B vaccine (HBV) microneedles because of its good water solubility, improved safety, and positive effect as shown in intramuscular administration of a liquid vaccine. RESULTS: All solid formulations with CTA 1 dissolved in in vivo mouse skin within 30 min, and they were successfully delivered into the skin. In experiments with mice, the addition of CTA1 led to improved IgG immune response compared to the use of an aluminum hydroxide-based formulation and intramuscular administration of HBV. In addition, CTA1 induced CD8 + T cell response as much as in which the aluminum hydroxide-based formulation induced. CONCLUSIONS: CTA1 is an adjuvant that satisfies both the delivery efficiency and the immunological characteristics required for vaccine microneedles. CTA1 will be used as a potential adjuvant through vaccine microneedles.

Gate Controlled Excitonic Emission in Quantum Dot Thin Films.

Formation of charged trions is detrimental to the luminescence quantum efficiency of colloidal quantum dot (QD) thin films as they predominantly undergo nonradiative recombination. In this regard, control of charged trion formation is of interest for both fundamental characterization of the quasi-particles and performance optimization. Using CdSe/CdS QDs as a prototypical material system, here we demonstrate a metal-oxide-semiconductor capacitor based on QD thin films for studying the background charge effect on the luminescence efficiency and lifetime. The concentration ratio of the charged and neutral quasiparticles in the QDs is reversibly controlled by applying a gate voltage, while simultaneous steady-state and time-resolved photoluminescence measurements are performed. Notably, the photoluminescence intensity is modulated by up to 2 orders of magnitude with a corresponding change in the effective lifetime. In addition, chip-scale modulation of brightness is demonstrated, where the photoluminescence is effectively turned on and off by the gate, highlighting potential applications in voltage-controlled electrochromics.

Self-Organized Phase-Composite Nanocrystal Solids with Superior Charge Transport.

Interparticle electronic coupling is essential for self-assembled colloidal nanocrystal (NC) solid semiconductors to fulfill their wide-tunable electrical and optoelectrical properties, but it has been limited by disorders. Here, a disorder-tolerant coupling approach is presented by synthesizing self-organized NC solids based on amorphous/nanocrystalline phase-composites. The ZnO amorphous matrix, which infills the space between the less regularly ordered ZnO NCs, enables robust electronic coupling between neighboring NCs via the resonant wave function overlap, leading to a disorder-tolerant resonant conducting state. Field-effect transistors based on phase-composite semiconductors show delocalized band-like transport with superior field-effect mobility values (∼75 cm2 V-1 s-1), compared to amorphous or polycrystalline ZnO semiconductors. Furthermore, the broad amorphous matrix can mitigate interfacial defects between crystalline regions through atomic relaxation, in contrast to narrow grain boundaries in polycrystalline films, resulting in a significantly low interface trap density for phase-composite NC solids. Density function theory calculations and quantum transport simulations using the nonequilibrium Green's function formalism elucidate the origins of superior and highly disorder-tolerant electron transport in phase-composite NC solids. Our report introduces a new class of NC solids complementary to the colloidal counterpart and will be applicable to CMOS-compatible emerging device technologies.

Role of Temperature-Dependent Interfacial Tension on Shear Wave Velocity for Energy Geosystems.

Interfacial tension varies with temperature. This paper investigates the effects of temperature-dependent interfacial tension on shear wave velocity. We designed a nylon cell equipped with bender elements in a cross-hole configuration to measure the shear wave velocity of nine sand-silt mixtures with different degrees of saturation (S = 0%, 2.5%, 5%, 10%, and 100%). All specimens were subjected to a temperature change from 10 °C to 1 °C. The results demonstrate that shear wave velocity tends to be very sensitive to changes in temperature at a low degree of saturation. Particle-scale analyses overlapped with the experimental results and captured the critical role of temperature-dependent interfacial tension in small-strain skeletal stiffness. In fact, the temperature should be considered during laboratory and field shear modulus measurements of the long-term performance of energy geosystems subjected to thermally induced repetitive loads.

A machine learning-assisted system to predict thyrotoxicosis using patients' heart rate monitoring data: a retrospective cohort study.

Previous studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)-assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients. HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with thyroid dysfunction. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML-assisted system predicted thyrotoxicosis of a patient at a given time point based on HR data and their HR-TFT data pair at another time point. Our ML-assisted system divided the 662 cases into either thyrotoxicosis and non-thyrotoxicosis and the performance was calculated based on the TFT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 86.14%, 85.92%, 52.41%, and 97.18%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 86.14%, 98.28%, 94.57%, and 95.32%, respectively. Our ML-assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen-Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis. Our ML-assisted system has demonstrated reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction, and the accuracy could be further improved by gathering more data. This predictive system has the potential to monitor the thyroid function status of patients with thyroid dysfunction by collecting heart rate data, and to determine the optimal timing for blood tests and treatment intervention.

Biodegradation behavior of acetylated lignin added polylactic acid under thermophilic composting conditions.

Acetylated lignin (AL) can improve compatibility with commercial plastic polymers compared to existing lignin and can be used as an effective additive for eco-friendly biocomposites. For this reason, AL can be effectively incorporated into polylactic acid (PLA)-based biocomposites, but its biodegradation properties have not been investigated. In this study, biodegradation experiments were performed under mesophilic and thermophilic conditions to determine the effect of AL addition on the biodegradation characteristics of PLA-based biocomposites. As a result, the PLA-based biocomposite showed a faster biodegradation rate in a thermophilic composting environment, which is higher than the glass transition temperature of PLA, compared to a mesophilic environment. 16S rDNA sequencing results showed that differences in microbial communities depending on mesophilic and thermophilic environments strongly affected the biodegradation rate of lignin/PLA biocomposites. Importantly, the addition of AL can effectively delay the thermophilic biodegradation of PLA biocomposites. As a result of tracking the changes in physicochemical properties according to the biodegradation period in a thermophilic composting environment, the main biodegradation mechanism of AL/PLA biocomposite hydrolysis. It proceeded with cleavage of the PLA molecular chain, preferential biodegradation of the amorphous region, and additional biodegradation of the crystalline region. Above all, adding AL can be proposed as an effective additive because it can minimize the decline in the mechanical properties of PLA and delay the biodegradation rate more effectively compared to existing kraft lignin (KL).

Enhancement of elongation at break and UV-protective properties of poly(lactic acid) film with cationic ring opening polymerized (CROP)-lignin.

In this study, the intrinsic brittleness of poly(lactic acid) (PLA) was overcome by chemical modification using ethyl acetate-extracted lignin (EL) via cationic ring-opening polymerization (CROP). The CROP was conducted to promote homopolymerization under starvation of the initiator (oxyrane). This method resulted in the formation of lignin-based polyether (LPE). LPE exhibited enhanced interfacial compatibility with nonpolar and hydrophobic PLA owing to the fewer hydrophilic hydroxyl groups and a long polyether chain. In addition, because of the UV-protecting and radical-scavenging abilities of lignin, LPE/PLA exhibited multifunctional properties, resulting in improved chemical properties compared with the neat PLA film. Notably, one of the LPE/PLA films (EL_MCF) exhibited excellent elongation at break of 297.7 % and toughness of 39.92 MJ/m3. Furthermore, the EL_MCF film showed superior UV-protective properties of 99.52 % in UVA and 88.95 % in UVB ranges, both significantly higher than those of the PLA film, without sacrificing significant transparency in 515 nm. In addition, the radical scavenging activity improved after adding LPE to the PLA film. These results suggest that LPEs can be used as plasticizing additives in LPE/PLA composite films, offering improved physicochemical properties.

USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity.

ETS2 is a member of the ETS family of transcription factors and has been implicated in the regulation of cell proliferation, differentiation, apoptosis, and tumorigenesis. The aberrant activation of ETS2 is associated with various human cancers, highlighting its importance as a therapeutic target. Understanding the regulatory mechanisms and interacting partners of ETS2 is crucial for elucidating its precise role in cellular processes and developing novel strategies to modulate its activity. In this study, we conducted binding assays using a human deubiquitinase (DUB) library and identified USP39 as a novel ETS2-binding DUB. USP39 interacts with ETS2 through their respective amino-terminal regions, and the zinc finger and PNT domains are not required for this binding. USP39 deubiquitinates ETS2 without affecting its protein stability. Interestingly, however, USP39 significantly suppresses the transcriptional activity of ETS2. Furthermore, we demonstrated that USP39 leads to a reduction in the nuclear localization of ETS2. Our findings provide valuable insights into the intricate regulatory mechanisms governing ETS2 function. Understanding the interplay between USP39 and ETS2 may have implications for therapeutic interventions targeting ETS2-related diseases, including cancer, where the dysregulation of ETS2 is frequently observed.

Strategic design of gold nanocatalysts for effective photocatalytic organic transformation.

We demonstrate the design strategy of free-standing Au nanocatalysts by correlating their physicochemical characteristics with photocatalytic performance. By tailoring the particle size and surface characteristics, we found that small Au nanocatalysts called Au nanoclusters with discrete energy levels are more effective than large metallic Au nanoparticles, while the microenvironments (e.g., charge status and hydrophilicity/hydrophobicity) around the surface of Au-nanoclusters are crucial in determining the performance. With the optimized Au nanocatalyst, under visible light, decarboxylative radical addition reactions for C-C bond formation (i.e., Giese reaction) were first achieved with high yields and further utilized for the preparation of one of the bioactive γ-aminobutyric acid derivatives, pregabalin (Lyrica®), demonstrating its potential in pharmaceutical applications.