Fabrication of albumin-Ti3C2 MXene quantum dots-based nanohybrids for breast cancer imaging and synergistic photo/chemotherapeutics.

Advancement in the development of new materials with theranostic and phototherapeutic potential along with receptiveness to external stimuli has been persistently inspiring oncology research. Herein, titanium carbide-based MXene quantum dots (FHMQDs) have been synthesized and modified to take advantage of stimuli-responsive behavior and target specificity for breast cancer cells. With a size of around 3 nm, the developed FHMQDs demonstrate high fluorescent emission at around 460 nm. With ∼90 % encapsulation efficiency of doxorubicin (DOX), the developed system also offers rapid DOX release behavior when encountering an acidic pH (5.4). Further, the in vitro assessment of the developed FHMQDs on MDA-MB 231 breast cancer cells presents excellent target specificity to cancer cells which was reflected by its high cytotoxicity against cancer cells. Additionally, the outstanding photodynamic efficiency of FHMQDs due to excessive Reactive Oxygen Species (ROS) generating ability along with apoptosis promoting capability of FHMQDs in cancer cells demonstrates a synergistic approach in cancer theranostics. Encouragingly, the fabricated FHMQDs also exhibited fluorescent labelling and bioimaging capacity which makes it an incredible platform that ensures theranostic excellence in breast cancer research.

Promoter mutation-independent TERT expression is related to immune-enriched milieu in papillary thyroid cancer.

Telomerase reverse transcriptase promoter mutation (pTERT MT) promotes human carcinogenesis via aberrant expression of telomerase reverse transcriptase (TERT). However, the tumorigenic impact of TERT expression independent of pTERT MT remains unclear despite numerous mechanisms of TERT being suggested. To tackle this issue, we employed comprehensive bioinformatics to assess biological variations noticed among different TERT expression mechanisms. Papillary thyroid cancer (PTC) with pTERT MT (pTERT MT PTC) presented aggressive clinical behavior and exhibited biological profiles associated with cellular immortality and genomic instability. PTC with TERT expression, but without pTERT MT (TERT (+) PTC), also exhibited poor clinicopathological characteristics and was enriched with immune responses. In accordance, c-MYC/E2F and nuclear factor kappa B (NFκB) were dominant transcription factors in pTERT MT PTC and TERT (+) PTC, respectively. Notably, we revealed TERT hypermethylated oncological region (THOR) as potential TERT expressing mechanism in TERT (+) PTC patients. Furthermore, three unique subtypes of papillary thyroid cancer were deciphered using combination of machine learning based scoring systems. Our proposed scoring system was clinically significant especially in microcarcinoma predicting survival outcomes and inferring therapeutic responses of radioactive iodine therapy. Finally, our analysis was expanded to endocrine-related cancers, unveiling various regulatory mechanisms of TERT with poor clinical outcomes and biological behaviors.

Relationship between job challenge and job performance in the Korean Army: The mediating effect of learning agility and the moderating effect of job autonomy.

This study aims to identify the relationship among job challenge, learning agility, job autonomy, and job performance based on job demand-resources model. In particular, this study examined the mediating role of learning agility in the relationship between Job challenge and job performance, which has rarely been conducted. Furthermore, the moderating effect of job autonomy as job resource was explored. The data collected were from army officers and noncommissioned officers (NCO) of the Korean Army (N = 425). We hypothesized that there is a positive relationship among Job challenge and learning agility, Job challenge and job performance, the mediating role of learning agility in the relationship between Job challenge and job performance, and the moderating role of job autonomy. As predicted, we found that Job challenge was positively related to learning agility and job performance. We also found a mediating effect of learning agility on the relationship between Job challenge and job performance. Furthermore, job autonomy moderated the positive relationship between Job challenge and learning agility, although the moderating effect of job autonomy between Job challenge and job performance was not significant. Finally, the indirect relationship between Job challenge and job performance, via learning agility, was stronger for the higher job autonomy group than for the lower job autonomy group. The, theoretical and practical contributions and suggestions for future studies on learning agility and job characteristics are discussed.

Anti-Melanogenic Effects of Cnidium monnieri Extract via p38 Signaling-Mediated Proteasomal Degradation of Tyrosinase.

Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 µg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 µg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.

Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Radiological manifestations and clinical findings of patients with oncologic and osteoporotic medication-related osteonecrosis of the jaw.

Medication-related osteonecrosis of the jaw (MRONJ) poses a challenging form of osteomyelitis in patients undergoing antiresorptive therapies in contrast to conventional osteomyelitis. This study aimed to compare the clinical and radiological features of MRONJ between patients receiving low-dose medications for osteoporosis and those receiving high-dose medications for oncologic purposes. The clinical, panoramic radiographic, and computed tomography data of 159 patients with MRONJ (osteoporotic group, n = 120; oncologic group, n = 39) who developed the condition after using antiresorptive medications for the management of osteoporosis or bone malignancy were analyzed. The osteoporotic group was older (75.8 vs. 60.4 years, p < 0.01) and had a longer duration of medication usage than the oncologic group (58.1 vs. 28.0 months, p < 0.01). Pus discharge and swelling were more common in the osteoporotic group (p < 0.05), whereas bone exposure was more frequent in the oncologic group (p < 0.01). The mandibular cortical index (MCI) in panoramic radiographs was higher in the osteoporotic group (p < 0.01). The mean sequestra size was larger in the oncologic group than in the osteoporotic group (15.3 vs. 10.6 mm, p < 0.05). The cured rate was significantly higher in the osteoporotic group (66.3% vs. 33.3%, p < 0.01). Oncologic MRONJ exhibited distinct clinical findings including rapid disease onset, fewer purulent signs, and lower cure rates than osteoporotic MRONJ. Radiological features such as sequestrum size on CT scan, and MCI values on panoramic radiographs, may aid in differentiating MRONJ in osteoporotic and oncologic patients.

Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages.

Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or AlphaFold-Multimer predictions. Using the quantitative assay LuTHy together with our machine learning algorithm, we identified high-confidence interactions among SARS-CoV-2 proteins for which we predicted three-dimensional structures using AlphaFold-Multimer. We employed VirtualFlow to target the contact interface of the NSP10-NSP16 SARS-CoV-2 methyltransferase complex by ultra-large virtual drug screening. Thereby, we identified a compound that binds to NSP10 and inhibits its interaction with NSP16, while also disrupting the methyltransferase activity of the complex, and SARS-CoV-2 replication. Overall, this pipeline will help to prioritize PPI targets to accelerate the discovery of early-stage drug candidates targeting protein complexes and pathways.

Development of carrageenan-immobilized lytic coliphage vB_Eco2571-YU1 hydrogel for topical delivery of bacteriophages in wound dressing applications.

Bacteriophages are employed as cost-effective and efficient antibacterial agents to counter the emergence of antibiotic-resistant bacteria and other host bacteria in phage therapy. The increasing incidence of skin wounds is a significant concern in clinical practice, especially considering the limitations of antibiotic therapy. Furthermore, the lack of an effective delivery system that preserves the stability of bacteriophages hampers their clinical implementation. In recent years, there has been a growing amount of research on bacteriophage applications in veterinary and biomedical sciences. In our study, lytic coliphage vB_Eco2571-YU1 was isolated against pathogenic Escherichia coli host bacteria, and hydrogel wound dressing materials were fabricated with marine polysaccharide carrageenan (carr-vB_Eco2571-YU1) for their antibacterial activity. Transmission electron microscopy (TEM) morphology identified it as a Myoviridae coliphage with an icosahedral head length and width of approximately 60 and 56.8 nm, respectively, and a tail length of 119.7 nm. The one-step growth curve of coliphage revealed a latent period of 10 min, a rise period of 15 min, and a burst size of 120 virions per cell. The bacteriolytic activity of unimmobilized coliphages was observed within 2 h; however, strain-specific phage resistance was acquired after 9 h. In contrast, carr-vB_Eco2571-YU1 showed a sharp decline in the growth of bacteria in the log phase after 2 h and did not allow for the acquisition of phage resistance by the E. coli strain. The stability of coliphage under different pH, temperature, osmolarity, detergents, and organic solvents was evaluated. We also studied the long-term storage of carr-vB_Eco2571-YU1 hydrogels at 4 °C and found that the titer value decreased during a time-dependent period of 28 days. These hydrogels were also found to be hemocompatible using a hemolysis assay. The addition of plasticizer (0.6 % (w/v)) to the carrageenan (2 % (w/v)) to prepare carr-vB_Eco2571-YU1 hydrogels showed a decrease in compressive strength with enhanced elasticity. This phage therapy using polymeric immobilization of bacteriophages is a promising next-generation wound dressing biomaterial alternative to conventional wound and skin care management.

Mechanisms of Wharton's Jelly-derived MSCs in enhancing peripheral nerve regeneration.

Warton's jelly-derived Mesenchymal stem cells (WJ-MSCs) play key roles in improving nerve regeneration in acellular nerve grafts (ANGs); however, the mechanism of WJ-MSCs-related nerve regeneration remains unclear. This study investigated how WJ-MSCs contribute to peripheral nerve regeneration by examining immunomodulatory and paracrine effects, and differentiation potential. To this end, WJ-MSCs were isolated from umbilical cords, and ANGs (control) or WJ-MSCs-loaded ANGs (WJ-MSCs group) were transplanted in injury animal model. Functional recovery was evaluated by ankle angle and tetanic force measurements up to 16 weeks post-surgery. Tissue biopsies at 3, 7, and 14 days post-transplantation were used to analyze macrophage markers and interleukin (IL) levels, paracrine effects, and MSC differentiation potential by quantitative real-time polymerase chain reaction (RT-qPCR) and immunofluorescence staining. The WJ-MSCs group showed significantly higher ankle angle at 4 weeks and higher isometric tetanic force at 16 weeks, and increased expression of CD206 and IL10 at 7 or 14 days than the control group. Increased levels of neurotrophic and vascular growth factors were observed at 14 days. The WJ-MSCs group showed higher expression levels of S100ß; however, the co-staining of human nuclei was faint. This study demonstrates that WJ-MSCs' immunomodulation and paracrine actions contribute to peripheral nerve regeneration more than their differentiation potential.

Inflammatory Activity of Epithelial Stem Cell Variants from Cystic Fibrosis Lungs Is Not Resolved by CFTR Modulators.

Rationale: CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs. Objectives: To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) lungs, harbor potentially pathogenic stem cell "variants" distinct from the normal p63/Krt5 lung stem cells devoted to alveolar fates, to identify specific variants that might contribute to the inflammatory state of CF lungs, and to assess the impact of CFTR genetic complementation or CFTR modulators on the inflammatory variants identified herein. Methods: Stem cell cloning technology developed to resolve pathogenic stem cell heterogeneity in COPD and idiopathic pulmonary fibrosis lungs was applied to end-stage lungs of patients with CF (three homozygous CFTR:F508D, one CFTR F508D/L1254X; FEV1, 14-30%) undergoing therapeutic lung transplantation. Single-cell-derived clones corresponding to the six stem cell clusters resolved by single-cell RNA sequencing of these libraries were assessed by RNA sequencing and xenografting to monitor inflammation, fibrosis, and mucin secretion. The impact of CFTR activity on these variants after CFTR gene complementation or exposure to CFTR modulators was assessed by molecular and functional studies. Measurements and Main Results: End-stage CF lungs display a stem cell heterogeneity marked by five predominant variants in addition to the normal lung stem cell, of which three are proinflammatory both at the level of gene expression and their ability to drive neutrophilic inflammation in xenografts in immunodeficient mice. The proinflammatory functions of these three variants were unallayed by genetic or pharmacological restoration of CFTR activity. Conclusions: The emergence of three proinflammatory stem cell variants in CF lungs may contribute to the persistence of lung inflammation in patients with CF with advanced disease undergoing CFTR modulator therapy.

Sexual orientation in transgender adults in the United States.

BACKGROUND: Sexual orientation refers to a person's enduring emotional, romantic, or sexual attractions to other people. Sexual orientation measures do not typically consider desires for, or sexual behavior with, transgender people. We describe measures inclusive of transgender people and characterize sexual orientation identity, behavior, and attraction in a representative sample of the U.S. transgender population. METHODS: Between April 2016-December 2018, a U.S. national probability sample of transgender (n = 274) and cisgender (n = 1,162) adults were invited to complete a self-administered web or mailed paper survey. We assessed sexual identity with updated response options inclusive of recent identity terms (e.g., queer), and revised sexual behavior and attraction measures that included transgender people. Multiple response options were allowed for sexual behavior and attraction. Weighted descriptive statistics and sexual orientation differences by gender identity groups were estimated using age-adjusted comparisons. RESULTS: Compared to the cisgender population, the transgender population was more likely to identify as a sexual minority and have heterogeneity in sexual orientation, behavior, and attraction. In the transgender population, the most frequently endorsed sexual orientation identities were "bisexual" (18.9%), "queer" (18.1%), and "straight" (17.6%). Sexually active transgender respondents reported diverse partners in the prior 5 years: 52.6% cisgender women (CW), 42.7% cisgender men (CM), 16.9% transgender women (TW), and 19.5% transgender men (TM); 27.7% did not have sex in the past 5 years. Overall, 73.6% were "somewhat"/ "very" attracted to CW, 58.3% CM, 56.8% TW, 52.4% TM, 59.9% genderqueer/nonbinary-females-at-birth, 51.9% genderqueer/nonbinary-males-at-birth. Sexual orientation identity, behavior, and attraction significantly differed by gender identity for TW, TM, and nonbinary participants (all p < 0.05). CONCLUSIONS: Inclusive measures of sexual orientation captured diverse sexual identities, partner genders, and desires. Future research is needed to cognitively test and validate these measures, especially with cisgender respondents, and to assess the relation of sexual orientation and health for transgender people.

Nasal cavity perforation by implant fixtures: case series with emphasis on panoramic imaging of nasal cavity extending posteriorly.

The nasal cavity is an important landmark when considering implant insertion into the anterior region of the maxillary arch. The perforation of implants into the nasal cavity may cause complications, such as implant migration, inflammation, or changes in nasal airflow; thus, precise assessment of the nasal cavity is mandatory.Three cases of nasal cavity perforation by dental implants are presented, including one case of implant fixture migration into the nasal cavity. On panoramic radiographs of the patients, the following common features were observed: the horizontal radiopaque line of the hard palate was observed to be inferior to or similar to that of the antral floor and the bone between the lateral wall of the nasal cavity and the medial wall of the maxillary sinus was emphasized in a triangular shape.When the maxillary sinus is small and alveolar bone resorption is severe, panoramic evaluation may cause overestimation of the available residual bone, particularly in the maxillary canine/premolar region. Therefore, the residual bone should be reevaluated three-dimensionally to measure the exact bony shape and volume.

Distinct Prognosis of Minimal Residual Disease According to Breast Cancer Subtype in Patients with Breast or Nodal Pathologic Complete Response After Neoadjuvant Chemotherapy.

PURPOSE: Few studies have reported on patient prognosis according to residual cancer burden after neoadjuvant chemotherapy (NAC). Herein, we evaluated the survival of patients based on residual disease after NAC to identify subpopulations with distinct prognoses. METHODS: We retrospectively reviewed 728 patients treated with NAC from 2010 to 2017. Patients were divided into four subgroups depending on post-surgical residual disease according to the staging system: pathological complete response (pCR) (ypT0/TisN0), minimal residual disease (MRD) (ypT1mi/T1aN0 or ypT0/Tis ypN0i+/N1mic), node-only pCR (≥ ypT1b ypN0), and breast-only pCR (ypT0/Tis ≥ ypN1a). Clinicopathological characteristics and survival outcomes were analyzed by adjusting for factors affecting survival. RESULTS: Overall, 50.4% (n = 367) of patients achieved pCR, with the MRD group accounting for 16.5% (n = 120). Although age and clinical stage were not different among the study groups, histologic grade, subtypes, chemotherapy response, and local treatment showed differences. Event-free survival (EFS) and overall survival (OS) demonstrated no significant difference between the pCR and MRD groups. In the multivariate analysis, pCR status was the only significant factor in EFS, and no statistical difference was noted between the pCR and MRD groups. However, clinical stage, pCR status, and subtype significantly affected the OS. MRD showed favorable outcomes in terms of both EFS and OS in all subtypes, except for those with triple-negative breast cancer (TNBC). CONCLUSION: Patients with MRD showed outcomes comparable to those of patients who achieved pCR and may be candidates for de-escalation of post-NAC treatment, except for those with a TNBC subtype.

Validation of ICD-10 hospital discharge diagnosis codes to identify incident and recurrent ischemic stroke from a US integrated healthcare system.

PURPOSE: This study validated incident and recurrent ischemic stroke identified by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10) hospital discharge diagnosis codes. METHODS: Using electronic health records (EHR) of adults (≥18 years) receiving care from Kaiser Permanente Southern California with ICD-10 hospital discharge diagnosis codes of ischemic stroke (I63.x, G46.3, and G46.4) between October 2015 and September 2020, we identified 75 patients with both incident and recurrent stroke events (total 150 cases). Two neurologists independently evaluated validity of ICD-10 codes through chart reviews. RESULTS: The positive predictive value (PPV, 95% CI) for incident stroke was 93% (95% CI: 88%, 99%) and the PPV for recurrent stroke was 72% (95% CI: 62%, 82%). The PPV for recurrent stroke improved after applying a gap of 20 days (PPV of 75%; 95% CI: 63%, 87%) or removing hospital admissions related to stroke-related procedures (PPV of 78%; 95% CI: 68%, 88%). CONCLUSION: The ICD-10 hospital discharge diagnosis codes for ischemic stroke showed a high PPV for incident cases, while the PPV for recurrent cases were less optimal. Algorithms to improve the accuracy of ICD-10 codes for recurrent ischemic stroke may be necessary.

AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.

Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays and AlphaFold-Multimer predictions. Using the quantitative assay LuTHy together with our machine learning algorithm, we identified high-confidence interactions among SARS-CoV-2 proteins for which we predicted three-dimensional structures using AlphaFold Multimer. We employed VirtualFlow to target the contact interface of the NSP10-NSP16 SARS-CoV-2 methyltransferase complex by ultra-large virtual drug screening. Thereby, we identified a compound that binds to NSP10 and inhibits its interaction with NSP16, while also disrupting the methyltransferase activity of the complex, and SARS-CoV-2 replication. Overall, this pipeline will help to prioritize PPI targets to accelerate the discovery of early-stage drug candidates targeting protein complexes and pathways.

Identification of GA20ox2 as a target of ATHB2 and TCP13 during shade response.

The shade avoidance syndrome (SAS) is a collective adaptive response of plants under shade highlighted by characteristic phenotypes such as hypocotyl elongation, which is largely mediated by concerted actions of auxin and GA. We identified ATHB2, a homeodomain-leucine zipper (HD-Zip) domain transcription factor known to be rapidly induced under shade condition, as a positive regulator of GA biosynthesis necessary for the SAS by transactivating the expression of GA20ox2, a key gene in the GA biosynthesis pathway. Based on promoter deletion analysis, EMSA and ChIP assay, ATHB2 appears to regulate the GA20ox2 expression as a direct binding target. We also found that the GA20ox2 expression is under negative control by TCP13, the effect of which can be suppressed by presence of ATHB2. Considering a rapid induction kinetics of ATHB2, this relationship between ATHB2 and TCP13 may allow ATHB2 to play a shade-specific activator for GA20ox by derepressing a pre-existing activity of TCP13.

Antibacterial, biocompatible, hemostatic, and tissue adhesive hydrogels based on fungal-derived carboxymethyl chitosan-reduced graphene oxide-polydopamine for wound healing applications.

In this study, we developed biocompatible, fungus-derived carboxymethyl chitosan (FCMCS)-reduced graphene oxide (rGO)-polydopamine (PDA)-polyacrylamide (PAM) (FC-rGO-PDA) hydrogels with excellent antibacterial, hemostatic, and tissue adhesive properties for wound healing applications. FC-rGO-PDA hydrogels were prepared by the alkali-induced polymerization of DA followed by the incorporation of GO and its reduction during the polymerization AM to form a homogeneously dispersed PAM network structure in FCMCS solution. The formation of rGO was verified using UV-Vis spectra. The physicochemical properties of hydrogels were characterized by FTIR, and SEM, water contact angle measurements, and compressive studies. SEM and contact angle measurements showed that hydrogels were hydrophilic with interconnected pores and a fibrous topology. In addition, hydrogels adhered well to porcine skin with an adhesion strength of 32.6 ± 1.3 kPa, . The hydrogels exhibited viscoelastic, good compressive (77.5 kPa), swelling, and biodegradation properties. An in vitro study using skin fibroblasts and keratinocytes cells showed the hydrogel had good biocompatibility. Testing against two model bacteria, viz. Staphylococcus aureus and E. coli revealed that the FC-rGO-PDA hydrogel has antibacterial activity. Furthermore, the hydrogel exhibited hemostasis properties. Overall, the developed FC-rGO-PDA hydrogel has antibacterial and hemostasis properties, high water holding capacity, and excellent tissue adhesive properties, which make it a promising candidate for wound healing applications.

A review on directional muscle cell growth in scaffolding biomaterials with aligned porous structures for cultivated meat production.

Scaffolds suitable for use in food products are essential in cultured meat production. Simultaneously, efforts are being undertaken to strengthen the scaffolding to improve cell proliferation, differentiation, and tissue formation. Muscle cells proliferate and differentiate according to the directional patterns of the scaffold, similar to natural tissue and native muscle tissue. Therefore, establishing an aligned pattern in the scaffolding architecture is vital for cultured meat applications. Recent studies on the fabrication of scaffolds with aligned porosity structures and their utility in manufacturing cultured meat are highlighted in this review. In addition, the directional growth of muscle cells in terms of proliferation and differentiation has also been explored, along with the aligned scaffolding architectures. The aligned porosity architecture of the scaffolds supports the texture and quality of meat-like structures. Although it is difficult to build adequate scaffolds for culturing meat manufactured from diverse biopolymers, it is necessary to develop novel methods to create aligned scaffolding structures. Furthermore, to avoid animal slaughter in the future, it will be imperative to adopt non-animal-based biomaterials, growth factors, and serum-free media conditions for quality meat production.

Eyebrow lifting using multidirectional absorbable thread.

BACKGROUND: Thread lifting is a common procedure in minimally invasive esthetic techniques and can also be used to raise the drooping soft tissue of the forehead by vertically inserting threads into the forehead. AIMS: This study aimed to examine the effect of forehead thread lifting on enhancing upper eyelid opening. METHODS: Fifteen patients were included in this study, all of whom underwent eyebrow thread lifting with MINT LIFT® UP. Photographs of the patients were taken before, immediately after, and 1 and 12 weeks after surgery. Changes in the position of the eyebrows and eyelids were measured. The paired t-test was used to determine the statistical significance of differences. RESULTS: At 1 week after surgery, the eyebrows were at a lower level compared with before surgery, and no significant changes in eye-opening were observed. However, at 12 weeks after surgery, the eyebrows and upper eyelids were both significantly elevated when compared to the preoperative state. CONCLUSIONS: Eyebrow lifting can be performed using multidirectional thread lifting.