Advances in Bioresorbable Triboelectric Nanogenerators.

With the growing demand for next-generation health care, the integration of electronic components into implantable medical devices (IMDs) has become a vital factor in achieving sophisticated healthcare functionalities such as electrophysiological monitoring and electroceuticals worldwide. However, these devices confront technological challenges concerning a noninvasive power supply and biosafe device removal. Addressing these challenges is crucial to ensure continuous operation and patient comfort and minimize the physical and economic burden on the patient and the healthcare system. This Review highlights the promising capabilities of bioresorbable triboelectric nanogenerators (B-TENGs) as temporary self-clearing power sources and self-powered IMDs. First, we present an overview of and progress in bioresorbable triboelectric energy harvesting devices, focusing on their working principles, materials development, and biodegradation mechanisms. Next, we examine the current state of on-demand transient implants and their biomedical applications. Finally, we address the current challenges and future perspectives of B-TENGs, aimed at expanding their technological scope and developing innovative solutions. This Review discusses advancements in materials science, chemistry, and microfabrication that can advance the scope of energy solutions available for IMDs. These innovations can potentially change the current health paradigm, contribute to enhanced longevity, and reshape the healthcare landscape soon.

Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin ß1.

BACKGROUND: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.

Tibial-sided Anterolateral Ligament Injuries Are Associated With Poor Healing and Residual Pivot Shift Testing After Anterior Cruciate Ligament Reconstruction.

PURPOSE: To investigate whether tibial-sided anterolateral ligament (ALL) injuries are associated with poor healing and residual pivot shift. METHODS: Patients who underwent anterior cruciate ligament reconstructions within postinjury 6 weeks from January 2008 to March 2021 were included. They had concomitant ALL injury confirmed by preoperative magnetic resonance imaging (MRI) and were followed for a minimum of 20 months. Preoperative ALL injury was graded by the Muramatsu classification, and postoperative ALL healing were graded by a modification of the Lee classification (good, partial, and nonvisualized). The patients were allocated to an improved group (IG) and an unimproved group (UG) on the basis of a comparison of pre- and postoperative MRI. ALL tear site, postoperative knee stability, Lysholm score, and Tegner activity scale (patient-reported outcomes [PROs]) were compared between the 2 groups. RESULTS: In total, 128 patients were enrolled; 94.5% patients achieved the minimal clinically important difference for PROs, respectively. The ALL was torn at the femoral side in 46.9% patients, at midsubstance in 31.2.%, and at tibial side in 21.9%, Preoperatively, 86 (67.2%) patients had a partial tear, and 42 (32.8%) patients had a complete tear. On the basis of the postoperative MRI appearances, 38 (29.7%) and 90 (70.3%) patients were allocated to the IG and UG, respectively. The tibial-side tears were significantly frequent in the UG (P = .032). Pivot shift showed a significantly greater incidence in the UG than IG (P = .004). Lachman test and PROs did not differ between the 2 groups. CONCLUSIONS: Tibial-sided ALL tears occurred in 18.7% of the UG compared with 3.2% of the IG, and 45.6% of the UG had a postoperative grade 1 or 2 pivot shift compared with 15.8% of the IG. Percentages of patients with the minimal clinically important difference for PROs did not differ between the 2 groups. However, the clinical relevance is limited by a high transfer bias. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Combined Anterolateral Ligament and Anterior Cruciate Ligament Injury Is Associated With Increased Lateral Femoral Condyle Ratio.

PURPOSE: to investigate the association between the lateral femoral condylar ratio (LFCR), the posterior tibial slope (PTS), and injury of the anterolateral ligament (ALL). METHODS: Inclusion criteria were patients with acute anterior cruciate ligament (ACL) tear after noncontact injury during sports from October 1997 to May 2021. The LFCR and PTS were measured, and injury of the ALL was evaluated. Patients were divided into 2 groups: isolated ACL tear (isolated group) and combined ACL with ALL tear (combined group). The LFCR and PTS were compared between the isolated and combined groups. For each risk factor, the receiver operating characteristic curve, the area under the curve (AUC), and its 95% confidence interval (CI) were calculated to determine the cutoff for detecting increased risk of ALL injury. RESULTS: There were 83 patients in the isolated group and 176 patients in the combined group. Demographics of the 2 groups did not differ significantly. The LFCR was significantly larger in the combined group than in the isolated group (P = .000). The PTS did not differ between the two groups (P = .405). The LFCR (odds ratio [OR] = 1.58; P = .000) was a significant factor. Age, body mass index, and PTS were not associated with an ALL injury. The AUC (0.79; 95% CI, 0.74-0.85) for the LFCR had a sensitivity of 73% and specificity of 76% to predict an ALL rupture. The calculated cutoff of 64.5 was associated with an increased risk for ALL rupture (OR = 8.65; 95% CI, 4.73-15.81) when compared with the isolated group. CONCLUSIONS: An increased LFCR was associated with the ALL injury. However, increased PTS was not associated with ALL injury. These findings need to be considered for clinicians in treating ACL tear patients at risk for an ALL injury. LEVEL OF EVIDENCE: III, retrospective comparative prognostic trial.

ISRIB plus bortezomib triggers paraptosis in breast cancer cells via enhanced translation and subsequent proteotoxic stress.

Despite the success of proteasome inhibitors (PIs) in treating hematopoietic malignancies, including multiple myeloma (MM), their clinical efficacy is limited in solid tumors. In this study, we investigated the involvement of the integrated stress response (ISR), a central cellular adaptive program that responds to proteostatic defects by tuning protein synthesis rates, in determining the fates of cells treated with PI, bortezomib (Bz). We found that Bz induces ISR, and this can be reversed by ISRIB, a small molecule that restores eIF2B-mediated translation during ISR, in both Bz-sensitive MM cells and Bz-insensitive breast cancer cells. Interestingly, while ISRIB protected MM cells from Bz-induced apoptosis, it enhanced Bz sensitivity in breast cancer cells by inducing paraptosis, the cell death mode that is accompanied by dilation of the endoplasmic reticulum (ER) and mitochondria. Combined treatment with ISRIB and Bz may shift the fate of Bz-insensitive cancer cells toward paraptosis by inducing translational rescue, leading to irresolvable proteotoxic stress.

PSMD14 Targeting Triggers Paraptosis in Breast Cancer Cells by Inducing Proteasome Inhibition and Ca2+ Imbalance.

PSMD14, a subunit of the 19S regulatory particles of the 26S proteasome, was recently identified as a potential prognostic marker and therapeutic target in diverse human cancers. Here, we show that the silencing and pharmacological blockade of PSMD14 in MDA-MB 435S breast cancer cells induce paraptosis, a non-apoptotic cell death mode characterized by extensive vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. The PSMD14 inhibitor, capzimin (CZM), inhibits proteasome activity but differs from the 20S proteasome subunit-inhibiting bortezomib (Bz) in that it does not induce aggresome formation or Nrf1 upregulation, which underlie Bz resistance in cancer cells. In addition to proteasome inhibition, the release of Ca2+ from the ER into the cytosol critically contributes to CZM-induced paraptosis. Induction of paraptosis by targeting PSMD14 may provide an attractive therapeutic strategy against cancer cells resistant to proteasome inhibitors or pro-apoptotic drugs.

Core-Shell ZnO@Microporous Organic Polymer Nanospheres as Enhanced Piezo-Triboelectric Energy Harvesting Materials.

Core-shell nanospheres were prepared by the homogeneous coating of piezoelectric ZnO nanorod aggregates with triboelectric microporous organic polymer (MOP). The small energy harvesting performance of ZnO@MOP was significantly enhanced, compared with those of ZnO and MOP, due to the piezoelectrification-induced polarization of inner ZnO and the enhanced generation of tribopositive charges of MOP. Piezo-triboelectric nanogenerators (PTENGs) fabricated with ZnO@MOP showed peak-to-peak voltages of up to 534 V and a maximum power density of 1.19 mW cm-2 . In addition, the PTENGs showed excellent durability for 30 000 cycles, demonstrating as efficient power sources for charging electrolytic capacitors and for operating 200 green light emitting diode bulbs.

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia.

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer's vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies.

Computed Tomography Staging of Osteonecrosis of the Femoral Head.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) usually affects patients younger than 50 years and frequently leads to collapse of the femoral head and subsequent osteoarthritis of the hip. Joint-preserving procedures are attempted in the early stages without collapse, while total hip arthroplasty (THA) is done during more advanced stages with femoral head collapse or a fracture in the necrotic portion. Thus, accurate staging of the disease is mandatory to decide therapeutic strategy. The purpose of this study is to determine the prevalence of occult fracture in the necrotic portion among osteonecrotic femoral heads, which were classified as Association Research Circulation Osseous (ARCO) stage 1 or 2 on radiographs. MATERIALS AND METHODS: A preoperative computer tomography (CT) scan was routinely performed to obtain an adequate cup position in patients undergoing THA at our institution. Radiographs and CT scans of 308 patients, who underwent unilateral THA due to ONFH from January 2011 to December 2014, were assessed by two orthopedic surgeons to compare the stage based on simple radiography and that based on CT scans. RESULTS: Among the 308 hips, which were classified as stage I or II lesions on simple radiography, fracture inside the necrotic portion was seen in 63 hips (20.5%) on CT scans. Fifty-nine of the 63 patients were followed for two to five years. Further collapse of the femoral head occurred in 41 patients, and 36 of them underwent THA during the follow up. CONCLUSION: In this study, 20.5% of hips classified as ARCO stage I or II on simple radiography were found to be ARCO stage III on CT imaging. When a joint-preserving treatment is considered for early stage ONFH, CT examination is necessary for more precise staging of the disease.

Lercanidipine Synergistically Enhances Bortezomib Cytotoxicity in Cancer Cells via Enhanced Endoplasmic Reticulum Stress and Mitochondrial Ca2+ Overload.

The proteasome inhibitor (PI), bortezomib (Btz), is effective in treating multiple myeloma and mantle cell lymphoma, but not solid tumors. In this study, we show for the first time that lercanidipine (Ler), an antihypertensive drug, enhances the cytotoxicity of various PIs, including Btz, carfilzomib, and ixazomib, in many solid tumor cell lines by inducing paraptosis, which is accompanied by severe vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. We found that Ler potentiates Btz-mediated ER stress and ER dilation, possibly due to misfolded protein accumulation, in MDA-MB 435S cells. In addition, the combination of Btz and Ler triggers mitochondrial Ca2+ overload, critically contributing to mitochondrial dilation and subsequent paraptotic events, including mitochondrial membrane potential loss and ER dilation. Taken together, our results suggest that a combined regimen of PI and Ler may effectively kill cancer cells via structural and functional perturbations of the ER and mitochondria.

Pyrrolidine dithiocarbamate reverses Bcl-xL-mediated apoptotic resistance to doxorubicin by inducing paraptosis.

Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX) resistance, leading to failure in chemotherapy. In addition, the clinical use of high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL-overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell lines with high Bcl-xL expression. Additionally, combined treatment with DOX and PDTC markedly retarded tumor growth in a Huh-7 HCC cell xenograft tumor model, compared to either mono-treatment. These results suggest that DOX/PDTC co-treatment may provide a safe and effective therapeutic strategy against malignant hepatoma cells with Bcl-xL-mediated apoptotic defects. We also found that induction of paraptosis, a cell death mode that is accompanied by dilation of the endoplasmic reticulum and mitochondria, is involved in this anti-cancer effect of DOX/PDTC. The intracellular glutathione levels were reduced in Bcl-xL-overexpressing Chang-L cells treated with DOX/PDTC, and DOX/PDTC-induced paraptosis was effectively blocked by pretreatment with thiol-antioxidants, but not by non-thiol antioxidants. Collectively, our results suggest that disruption of thiol homeostasis may critically contribute to DOX/PDTC-induced paraptosis in Bcl-xL-overexpressing cells.

Association of Increased Lateral Femoral Condylar Ratio With Lateral Meniscus Posterior Root Tear in Noncontact ACL Injury.

Background: In the setting of anterior cruciate ligament (ACL) injury, lateral meniscus posterior root tears (LMPRTs) are less readily diagnosed on preoperative magnetic resonance imaging (MRI). Therefore, to predict LMPRTs in ACL injuries, it is necessary to understand the risk factors associated with them. Purpose/Hypothesis: The purpose of this study was to investigate the association of lateral femoral condylar ratio (LFCR) with LMPRTs in ACL injuries. It was hypothesized that an increased LFCR would be associated with LMPRTs in noncontact ACL injuries. Study Design: Cohort study; Level of evidence, 3. Methods: Enrolled were consecutive patients who underwent primary acute (<6 weeks from injury) ACL reconstruction after noncontact injury and had LMPRT confirmed on preoperative MRI and arthroscopically (combined group; n = 62) as well as patients who underwent isolated acute ACL reconstruction (isolated group; n = 80) who were matched to the combined group by age, height, and body mass index (BMI). All patients underwent surgery between January 1999 and November 2021. LFCR and posterior tibial slope (PTS) were measured and compared between the isolated and combined groups. The area under the receiver operating characteristic curve (AUC) was calculated to determine the cutoff for detecting increased risk of LMPRTs. Results: The demographic characteristics of the 2 groups did not differ significantly, nor did the PTS. The LFCR was a significant factor (odds ratio [OR], 1.23; P = .001) associated with LMPRT. Patient age, height, BMI, and PTS were not associated with LMPRT. The AUC (0.66; 95% CI, 0.57-0.75) for LFCR had a sensitivity of 39% and specificity of 90% to predict LMPRT. The calculated cutoff associated with an increased risk for LMPRT when compared with the isolated group was 67.0% (OR, 4.98; 95% CI, 2.10-11.79). Conclusion: Increased LFCR was associated with the presence of LMPRTs in patients with acute ACL injuries. The LFCR may provide surgeons with additional information regarding the risk of having a concomitant LMPRT when planning ACL reconstructions.

Characteristics of impacted mandibular third molar-related lesions.

Objectives: This study identifies factors for differential diagnosis among lesions by retrospectively comparing panoramic and cone-beam computed tomography images and analyzing the characteristics of lesions associated with impacted mandibular third molars (IMTs). Materials and Methods: A retrospective cohort study was conducted in patients who simultaneously underwent IMT extraction surgery and related benign tumor resection or cyst enucleation at our institution from 2017 to 2021. To compare the characteristics of each group, two comparative analyses were conducted. The first comparison considered the most frequently observed lesions associated with IMTs: dentigerous cysts, odontogenic keratocysts (OKCs), and ameloblastoma. The second comparison involved placing dentigerous cysts, which have a relatively low recurrence rate, into group A and placing OKC, ameloblastoma, and odontogenic myxoma, which have high recurrence rates, into group B. Results: Significant differences in the size of the lesion were found in the order of ameloblastoma, OKC, and dentigerous cyst (P <0.05). The buccolingual width of ameloblastoma differed significantly from that of the other groups, with no significant difference observed between the OKCs and dentigerous cysts (P=0.083). Conclusion: Patient age and lesion size differed significantly among lesion types associated with IMTs, with younger age and larger lesions for OKCs and odontogenic tumors. OKCs are likely to have a larger mesiodistal width than dentigerous cysts. The buccolingual width of ameloblastomas was larger than those of dentigerous cysts and OKCs.

Radio frequency hyperthermia system for skin tightening effect by filled waveguide aperture antenna with compact metamaterials.

Radio frequency (RF) hyperthermia focuses on raising the target area temperature to a value exceeding 45°C. Collagen is stimulated when the temperature rises to 45°C at the dermal layer, resulting in skin tightening. However, most studies on RF hyperthermia have focused on tumor ablation or using electrodes to radiate an electromagnetic field, which is highly inefficient. This study proposed a non-invasive RF hyperthermia skin-tightening system with a compact metamaterial-filled waveguide aperture antenna. The proposed RF system increased the temperature by 11.6°C and 35.3°C with 20 and 80 W of 2.45 GHz RF power, respectively, within 60 s and exhibited a very focused effective area. Furthermore, a metamaterial was proposed to reduce the size of the waveguide aperture antenna and focus the electromagnetic field in the near-field region. The proposed metamaterial-filled waveguide aperture antenna was compact, measuring 10 mm × 17.4 mm, with a peak gain of 2.2 dB at 2.45 GHz. The measured hyperthermia performance indicated that the proposed RF system exhibited better power- and time-efficient hyperthermia performance than other RF hyperthermia systems in the cosmetic skin lifting commercial market. The proposed RF hyperthermia systems will be applied into a new generation of beauty cosmetic devices.

Intravascular papillary endothelial hyperplasia in the lungs of a wild Korean raccoon dog.

A male Korean raccoon dog of unknown age was rescued and placed at the Daejeon Wildlife Rescue Center, Korea. Physical examination revealed severe emaciation and dehydration, as well as thick crusts and alopecia over most of the body. During medical care, the animal died and was submitted for postmortem examination. Firm, brown-red lesions of various sizes were observed on the surface of the lungs. In cross-sections of the lungs, pulmonary vessels were thickened and dilated, with white irregular papillary luminal projections. Histologically, pulmonary blood vessels were severely hyperplastic, characterized by thickened dilated walls and fibrous papillary projections covered with a single layer of endothelial cells (ECs). Hyperplastic fibrous connective tissue was confirmed by Masson trichrome staining. The ECs expressed CD31. We diagnosed the lesion as intravascular papillary endothelial hyperplasia, a unique non-neoplastic reactive process that has not been reported previously in pulmonary vessels of canids, equids, or felids, to our knowledge.

Retrospective analysis on prognosis of oral cancer patients according to surgical approaches for effective cancer ablation: swing approach versus visor approach.

BACKGROUND: For the surgical treatment of oral cancer, it is sometimes necessary to expand intraoral access within the oral cavity. The "swing approach" that involves lip splitting of the mandible and temporary mandibular osteotomy and the "visor approach" that does not split the lower lip and mandible are mainly used. This study analyzed postoperative outcomes such as complications, recurrence rate, and survival rate by these two approaches. The goal of this study is to evaluate the surgical outcomes of patients using these two approaches, to propose effective perioperative management for oral cancer surgery, and to compare the prognosis of oral cancer patients. MATERIALS AND METHODS: From 2005 to 2020, 29 patients who underwent surgery at the Department of Oral and Maxillofacial Surgery of Pusan National University Dental Hospital for oral cancer lesions occurred in the mandible, floor of mouth, and tongue were selected for the study. Based on the surgical approach used, a chart review was conducted on various prognostic clinical factors such as the patients' sex and age, primary site, TNM stage, histopathologic grade, recurrence and metastasis, postoperative survival rate, adjuvant chemo-radiation therapy, satisfaction with aesthetics/function/swallowing, length of hospital stay, tracheostomy and its duration, and neck dissection and its type. Statistical analysis was conducted using SPSS 25.0 (SPSS Inc., Chicago, IL) through Fisher's exact t-test. RESULT: There was no statistically significant difference between two groups in terms of clinical and pathological findings, such as survival rate, the need for adjuvant therapies, and the local recurrence rate. Although better outcomes were observed in terms of function, aesthetics, and postoperative complications in the group with visor approach, there was still no statistically significant difference between two groups. However, the duration of hospital stay was shorter in the visor approach group. CONCLUSION: There was no statistically significant difference in clinical prognostic factors between the swing approach and the visor approach. Therefore, when choosing between the two approaches for the ablation of oral cancer, it is considered to select the surgical priority approach that can be easy access based on the size and location of the lesion. The visor approach had advantages of aesthetics and healing period.

Polyurethanes synthesized using biomass-derived furan diols as sustainable triboelectric materials.

This work shows that various polyurethanes (FPUs) prepared using biomass-derived furan diols can be applied as promising tribopositive materials. The elastic FPUs having appropriate glass transition temperature (Tg) could be incorporated into polyethylene terephthalate (PET) fabrics to form FPU/PET films. The optimal FPU-4/PET film showed promising triboelectric performance with output voltages (Vp-p) up to 405 V and a maximum power density (Pmax) of 32 mW cm-2.

Highly efficient microbial inactivation enabled by tunneling charges injected through two-dimensional electronics.

Airborne pathogens retain prolonged infectious activity once attached to the indoor environment, posing a pervasive threat to public health. Conventional air filters suffer from ineffective inactivation of the physics-separated microorganisms, and the chemical-based antimicrobial materials face challenges of poor stability/efficiency and inefficient viral inactivation. We, therefore, developed a rapid, reliable antimicrobial method against the attached indoor bacteria/viruses using a large-scale tunneling charge-motivated disinfection device fabricated by directly dispersing monolayer graphene on insulators. Free charges can be stably immobilized under the monolayer graphene through the tunneling effect. The stored charges can motivate continuous electron loss of attached microorganisms for accelerated disinfection, overcoming the diffusion limitation of chemical disinfectants. Complete (>99.99%) and broad-spectrum disinfection was achieved <1 min of attachment to the scaled-up device (25 square centimeters), reliably for 72 hours at high temperature (60°C) and humidity (90%). This method can be readily applied to high-touch surfaces in indoor environments for pathogen control.

RNA-Seq of an LPS-Induced Inflammation Model Reveals Transcriptional Profile Patterns of Inflammatory Processes.

The LPS-induced inflammation model is widely used for studying inflammatory processes due to its cost-effectiveness, reproducibility, and faithful representation of key hallmarks. While researchers often validate this model using clinical cytokine markers, a comprehensive understanding of gene regulatory mechanisms requires extending investigation beyond these hallmarks. Our study leveraged multiple whole-blood bulk RNA-seq datasets to rigorously compare the transcriptional profiles of the well-established LPS-induced inflammation model with those of several human diseases characterized by systemic inflammation. Beyond conventional inflammation-associated systems, we explored additional systems indirectly associated with inflammatory responses (i.e., ISR, RAAS, and UPR) using a customized core inflammatory gene list. Our cross-condition-validation approach spanned four distinct conditions: systemic lupus erythematosus (SLE) patients, dengue infection, candidemia infection, and staphylococcus aureus exposure. This analysis approach, utilizing the core gene list aimed to assess the model's suitability for understanding the gene regulatory mechanisms underlying inflammatory processes triggered by diverse factors. Our analysis resulted in elevated expressions of innate immune-associated genes, coinciding with suppressed expressions of adaptive immune-associated genes. Also, upregulation of genes associated with cellular stresses and mitochondrial innate immune responses underscored oxidative stress as a central driver of the corresponding inflammatory processes in both the LPS-induced and other inflammatory contexts.

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.