HRD1 promotes non-small cell lung carcinoma metastasis by blocking autophagy-mediated MIEN1 degradation.

Dysregulation of autophagy has been implicated in the development of many diseases, including cancer. Here, we revealed a novel function of the E3 ubiquitin ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis by regulating autophagy. Mechanistically, HRD1 inhibits autophagy by promoting ATG3 ubiquitination and degradation. Additionally, a pro-migratory and invasive factor, MIEN1 (migration and invasion enhancer 1), was found to be autophagically degraded upon HRD1 deficiency. Importantly, expression of both HRD1 and MIEN1 are upregulated and positively correlated in lung tumors. Based on these results, we proposed a novel mechanism of HRD1 function that the degradation of ATG3 protein by HRD1 leads to autophagy inhibition and MIEN1 release, thus promoting NSCLC metastasis. Therefore, our findings provided new insights into the role of HRD1 in NSCLC metastasis and new therapeutic targets for lung cancer treatment.

Human papillomavirus infections among women with cervical lesions and cervical cancer in Yueyang, China: a cross-sectional study of 3674 women from 2019 to 2022.

PURPOSE: To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. METHODS: A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. RESULTS: The total HPV prevalence was 74.69% (95% CI 73.28-76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53-68.77%), 80.78% (580/718, 95% CI 77.89-83.67%), 83.88% (483/576, 95% CI 80.84-86.87%), and 86.81% (408/470, 95% CI 83.74-89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89-50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50-59 years, 40-49 years, and 40-49 years, respectively. CONCLUSION: The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.

miR-940 modulates CD47 to suppress biological functions of lung adenocarcinoma cells.

OBJECTIVE: mir-940 and CD47 play regulatory and immunoregulatory roles in lung cancer. While previous study found that the expression of mir-940 decreased, associated with the increasing of CD47 in lung adenocarcinoma. However, their inherent correlations remain elusive. Herein, this experiment intends to search for the relevant molecular mechanisms regulating the biological function of non-small cell lung cancer. METHODS: The cancer and adjacent tissue samples were collected from 20 pairs of newly diagnosed non-small cell lung cancer patients without applying radiotherapy and chemotherapy. We performed immunohistochemistry containing 45 lung adenocarcinoma tissues to investigate the relationship between the clinicopathological features and CD47 expression. The expressions of mir-940 and CD47 were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Lung epithelial and lung adenocarcinoma (A549, H1299, GLC-82, PC-9) cell lines were cultured to detect the expression of mir-940 and CD47 molecules in each cell line. According to the expression situation, 2 cell lines were selected for mimic and siRNA transfection, and the transfection efficiency was also verified by qRT-PCR and western blot. CCK-8, transwell migration, transwell invasion, and colony formation assays were used to detect the changes in biological functions of lung adenocarcinoma cells after transfection, such as enhanced proliferation, migration, invasion, and cloning. The changes of related protein molecules after transfection were detected by western blot. The dual-luciferase experiment verified the targeting regulation relationship between mir-940 and CD47. Finally, flow cytometry analysis of apoptosis and cell cycle were carried out to detect apoptosis cells and change phase of cell cycle distribution. RESULTS: CD47 expression was not associated with clinicopathologic factors in lung adenocarcinoma. The proliferation, migration, invasion, and cloning abilities of lung adenocarcinoma cells were weakened after transfection with mir-940 mimic and siRNA-CD47. Overexpression of CD47 could promote proliferation, migration, invasion, cloning abilities, reduce apoptosis rate and attenuate the antitumor effect of mir-940 on lung adenocarcinoma. Dual luciferase experiments confirmed that mir-940 can target CD47 molecules. CONCLUSION: mir-940 can inhibit the biological function of lung adenocarcinoma cells by targeting CD47.

Select Your Own Counterparts: Self-Supervised Graph Contrastive Learning With Positive Sampling.

Contrastive learning (CL) has emerged as a powerful approach for self-supervised learning. However, it suffers from sampling bias, which hinders its performance. While the mainstream solutions, hard negative mining (HNM) and supervised CL (SCL), have been proposed to mitigate this critical issue, they do not effectively address graph CL (GCL). To address it, we propose graph positive sampling (GPS) and three contrastive objectives. The former is a novel learning paradigm designed to leverage the inherent properties of graphs for improved GCL models, which utilizes four complementary similarity measurements, including node centrality, topological distance, neighborhood overlapping, and semantic distance, to select positive counterparts for each node. Notably, GPS operates without relying on true labels and enables preprocessing applications. The latter aims to fuse positive samples and enhance representative selection in the semantic space. We release three node-level models with GPS and conduct extensive experiments on public datasets. The results demonstrate the superiority of GPS over state-of-the-art (SOTA) baselines and debiasing methods. In addition, the GPS has also been proven to be versatile, adaptive, and flexible.

Synergistic Bipolar Irreversible Electroporation for Tumor Ablation without Muscle Contraction.

Irreversible electroporation (IRE) has emerged as a promising modality for tumor ablation, leveraging the controlled application of electrical pulses to induce cell death. However, the associated muscle contractions during the procedure pose challenges. This study introduces a novel approach, termed Synergistic Bipolar Irreversible Electroporation (SBIRE), aimed at achieving tumor ablation without the undesirable side effect of muscle contraction. SBIRE involves the simultaneous application of nanosecond bipolar electrical pulses (±1600 V per 0.2 cm or ±8000 V per 1 cm, ±500 ns, "+" to "-" delay 1 µs, "-" to "+" delay 200 µs, 5 cycles) and microsecond bipolar electrical pulses (±300 V per 0.2 cm or ±1500 V per 1 cm, ±2 µs, "+" to "-" delay 2 µs, "-" to "+" delay 1000 µs, 25 cycles), strategically designed to synergistically target tumor cells while minimizing the impact on adjacent muscle tissue. The experimental setup includes in vitro and in vivo studies utilizing tumor cells and animal models to assess the efficacy of SBIRE. Preliminary results demonstrate the effectiveness of SBIRE in inducing irreversible electroporation within the tumor, leading to cell death, and the ablation effect is better than other parameter forms (24.41±0.23 mm2 (SBIRE group) vs 12.93±0.31 mm2 (ns group), 6.55±0.23 mm2 (µs group), 19.54±0.25 mm2 (ns+µs group), p<0.0001). Notably, muscle contraction is significantly reduced compared to traditional IRE procedures, highlighting the potential of SBIRE to enhance patient comfort and procedural success. The development of SBIRE represents a significant advancement in the field of tumor ablation, addressing a fundamental limitation associated with muscle contraction during IRE. This technique not only offers a valuable and promising approach to tumor treatment but also holds promise for minimizing procedural side effects.

CCT6A promotes cell proliferation in colon cancer by targeting BIRC5 associated with p53 status.

Chaperonin-containing TCP1 (CCT) is a multi-subunit complex, known to participate the correct folding of many proteins. Currently, the mechanism underlying CCT subunits in cancer progression is incompletely understood. Based on data analysis, the expression of CCT subunit 6 A (CCT6A) is found higher than the other subunits of CCT and correlated with an unfavorable prognosis in colon cancer. Here, we find CCT6A silencing suppresses colon cancer proliferation and survival phenotype in vitro and in vivo. CCT6A plays a role in cellular process, including the cell cycle, p53, and apoptosis signaling pathways. Further investigations have shown direct binding between CCT6A and both Wtp53 and Mutp53, and BIRC5 is found to act downstream of CCT6A. The highlight is that CCT6A inhibition significantly reduces BIRC5 expression independent of Wtp53 levels in Wtp53 cells. Conversely, in Mutp53 cells, downregulation of BIRC5 by CCT6A inhibition mainly depends on Mutp53 levels. Additionally, combined CCT6A inhibition and Wtp53 overexpression in Mutp53 cell lines effectively suppresses cell proliferation. It is concluded CCT6A is a potential oncogene that influences BIRC5 through distinct pathways in Wtp53 and Mutp53 cells.

A Randomised, Multicentre, Phase II Trial of Camrelizumab with or without Metastasis-directed Stereotactic Body Radiotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma.

PURPOSE: To investigate the efficacy of metastasis-directed therapy (MDT) when added to camrelizumab (Cam) in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). METHODS: We conducted a randomised, controlled, multicentre, phase II trial in 3 centres from China (NCT04830267). Patients with R/M-NPC, without prior exposure to immunotherapy, who presented with ≥2 lesions, and at least 1 measurable lesion were randomised 1:1 to either Cam alone or Cam plus MDT (Cam+MDT). Patients randomised to the MDT group must have 1 lesion that is amendable to stereotactic body radiotherapy (SBRT) prescribed to 27Gy in 3 fractions every other day. Primary endpoint was objective response rate (ORR) of unirradiated lesions by RECIST v1.1. RESULTS: Between April 2021 and August 2023, 39 patients were randomly assigned to receive either Cam (n=20) or Cam+MDT (n=19). 17/39 (43.6%) patients had oligometastatic disease (≤3 lesions); 18/39 (46.2%) had liver involvement; 3/39 (7.7%) had locoregional recurrent disease. ORR of unirradiated lesions did not differ between the treatment groups (26.3% [Cam+MDT] vs 30.0% [Cam], P=1.0). DCR of unirradiated lesions was 73.7% in the Cam+MDT group compared with 60.0% in the Cam group (P=0.571). After a median follow-up of 25.8 months, median progression-free survival was 9.3 (95% CI: 6.2-NR) months in the Cam+MDT group and 8.8 (95% CI: 3.3-NR) months in the Cam group (P=0.750). Exploratory analyses suggested a longer overall survival (OS) with Cam+MDT for patients with >3 lesions (HR 0.23 [95% CI: 0.07-0.77], P=0.009). G3 and above adverse events were comparable between the treatment groups (15.8% [Cam+MDT] vs 20.0% [Cam]). Overall rate of capillary proliferation was 17.9% (7/39) on the trial. CONCLUSIONS: Our study did not meet its primary endpoint of superior ORR of unirradiated lesions with the addition of MDT to Cam in patients with R/M-NPC.

Bit Reduction for Locality-Sensitive Hashing.

Locality-sensitive hashing (LSH) has gained ever-increasing popularity in similarity search for large-scale data. It has competitive search performance when the number of generated hash bits is large, reversely bringing adverse dilemmas for its wide applications. The first purpose of this work is to introduce a novel hash bit reduction schema for hashing techniques to derive shorter binary codes, which has not yet received sufficient concerns. To briefly show how the reduction schema works, the second purpose is to present an effective bit reduction method for LSH under the reduction schema. Specifically, after the hash bits are generated by LSH, they will be put into bit pool as candidates. Then mutual information and data labels are exploited to measure the correlation and structural properties between the hash bits, respectively. Eventually, highly correlated and redundant hash bits can be distinguished and then removed accordingly, without deteriorating the performance greatly. The advantages of our reduction method include that it can not only reduce the number of hash bits effectively but also boost retrieval performance of LSH, making it more appealing and practical in real-world applications. Comprehensive experiments were conducted on three public real-world datasets. The experimental results with representative bit selection methods and the state-of-the-art hashing algorithms demonstrate that the proposed method has encouraging and competitive performance.

Imaging Progression Under Low Respiratory Viral Load of SARS-CoV-2 Omicron Variant Infection: A Retrospective Study in China.

Purpose: To investigate the computed tomography (CT) findings of SARs-CoV-2 Omicron variant in relation to respiratory viral loads determined by cycle threshold values in reverse-transcription polymerase chain reaction (RT-PCR). Materials and Methods: From October 2022 to November 2022, 74 hospitalized patients with Omicron were included in this retrospective study. The radiological features, CT involvement scores in relation to the respiratory viral load, and factors associated with imaging progression (IP) after the RT-PCR results turned negative were analyzed. Results: The most common CT patterns of Omicron were multiple round-like or patchy ground-glass opacity (GGO) or mixed GGO in the peripheral or diffuse areas. The grading of CT involvement scores exhibited an inverse pattern compared to viral loads from day 1 to day 8 and from day 13 to day 20 after diagnosis. Among the 65 patients with complete imaging data, 45 (69.23%) showed IP with clinical warning indicators of disease exacerbation negative in 34 and positive in 11. Patients with IP were older than those with non-IP (NIP); the erythrocyte sedimentation rates, procalcitonin levels, and D-dimer levels on admission of patients with IP were significantly higher than those of patients with NIP, whereas the immunoglobulin (Ig) G antibody level on admission and CT involvement score on initial CT of patients with IP were significantly lower than those of patients with NIP (all P < 0.05). Conclusion: For patients with Omicron, the IP of lung abnormalities is common when the viral load decreases. Under these circumstances, paying attention to clinical warming indicators of disease progression may contribute to better patient management and the mitigation of severe pneumonia.

Anomaly Detection With Representative Neighbors.

Identifying anomalies from data has attracted increasing attention in recent years due to its broad range of potential applications. Although many efforts have been made for anomaly detection, how to effectively handle high-dimensional data and how to exactly explore neighborhood information, a fundamental issue in anomaly detection, have not yet received sufficient concerns. To circumvent these challenges, in this article, we propose an effective anomaly detection method with representative neighbors for high-dimensional data. Specifically, it projects the high-dimensional data into a low-dimensional space via a sparse operation and explores representative neighbors with a self-representation learning technique. The neighborhood information is then transformed into similarity relations, making the data converge or disperse. Eventually, anomalies are discriminated by a tailored graph clustering technique, which can effectively reveal structural information of the data. Extensive experiments were conducted on ten public real-world datasets with 11 popular anomaly detection algorithms. The results show that the proposed method has encouraging and promising performance compared to the state-of-the-art anomaly detection algorithms.

Bioinspired Self-Standing, Self-Floating 3D Solar Evaporators Breaking the Trade-Off between Salt Cycle and Heat Localization for Continuous Seawater Desalination.

Facing the global water shortage challenge, solar-driven desalination is considered a sustainable technology to obtain freshwater from seawater. However, the trade-off between the salt cycle and heat localization of existing solar evaporators (SE) hinders its further practical applications. Here, inspired by water hyacinth, a self-standing and self-floating 3D SE with adiabatic foam particles and aligned water channels is built through a continuous directional freeze-casting technique. With the help of the heat insulation effect of foam particles and the efficient water transport of aligned water channels, this new SE can cut off the heat transfer from the top photothermal area to the bulk water without affecting the water supply, breaking the long-standing trade-off between salt cycle and heat localization of traditional SEs. Additionally, its self-standing and self-floating features can reduce human maintenance. Its large exposure height can increase evaporation area and collect environmental energy, breaking the long-standing limitation of solar-to-vapor efficiency of conventional SEs. With the novel structure employed, an evaporation flux of 2.25 kg m-2 h-1 , and apparent solar-to-vapor efficiency of 136.7% are achieved under 1 sun illumination. This work demonstrates a new evaporator structure, and also provides a key insight into the structural design of next-generation salt-tolerant and high-efficiency SEs.

Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles.

Aged cells have declined regenerative ability when subjected to environmental insult. Here we elucidate the mechanism by which mechanical stimulus induces hair regeneration at the microenvironmental regulation level using the hair plucking and organoid culture models. We observed that the skin cells harvested from post-plucking day 3 (PPD3) have the best self-organizing ability during skin organoid culture and have the highest hair regeneration upon transplantation. By bulk RNA sequencing (RNA-seq) and single-cell RNA-seq analysis and in situ hybridization, we identified that the chemokine signaling pathway genes including CCL2 are significantly increased in the skin at PPD3 and in skin organoid cultures. Immunostaining shows that the PPD3 skin epithelial cells have increased multipotency, which is verified by the ability to self-organize to form epidermal aggregates during organoid culture. By adding CCL2 recombinant protein to the organoid culture using an environmental reprogramming protocol, we observed the PPD0 adult skin cells, which lose their regenerative ability can self-organize in organoid culture and regenerate hair follicles robustly upon transplantation. Our study demonstrates that CCL2 functions in immune regulation of hair regeneration under mechanical stimulus, and enhances cell multipotency during organoid culture. This provides a therapeutic potential for future clinical application.

Comparing T- and B-cell responses to COVID-19 vaccines across varied immune backgrounds.

The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide. A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages, while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells. However, specific T-cell responses remain largely unaffected by the mutations, indicating that T-cell-mediated cellular immunity can still provide protection. Moreover, the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo, which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1. These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies. The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health. The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants. Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.

A mutual neighbor-based clustering method and its medical applications.

Clustering analysis has been widely used in various real-world applications. Due to the simplicity of K-means, it has become the most popular clustering analysis technique in reality. Unfortunately, the performance of K-means heavily relies on initial centers, which should be specified in prior. Besides, it cannot effectively identify manifold clusters. In this paper, we propose a novel clustering algorithm based on representative data objects derived from mutual neighbors to identify different shaped clusters. Specifically, it first obtains mutual neighbors to estimate the density for each data object, and then identifies representative objects with high densities to represent the whole data. Moreover, a concept of path distance, deriving from a minimum spanning tree, is introduced to measure the similarities of representative objects for manifold structures. Finally, an improved K-means with initial centers and path-based distances is proposed to group the representative objects into clusters. For non-representative objects, their cluster labels are determined by neighborhood information. To verify the effectiveness of the proposed method, we conducted comparison experiments on synthetic data and further applied it to medical scenarios. The results show that our clustering method can effectively identify arbitrary-shaped clusters and disease types in comparing to the state-of-the-art clustering ones.

Biomimetic hydrophobic plastic foams with aligned channels for rapid oil absorption.

Although many oil absorption materials have been developed, it still remains a great challenge to achieve rapid absorption and efficient recovery. Over the past decade, research has focused on the development of freeze casting technology using water as a solvent. The materials prepared by this method have poor water resistance and are difficult to apply to oil absorption in aqueous environments. Here, an organic solvent freeze casting strategy is proposed to fabricate ultralight hydrophobic plastic foams with aligned channel structures. Through microscopy in situ observation, we revealed the growth morphology of ice crystals during directional freezing process. Moreover, aligned porous foams with various channel sizes are fabricated by regulating the cooling rate. We found that organic solvent-assisted freeze casting can enhance the hydrophobicity of the matrix material. These aligned porous foams exhibit excellent liquid absorption performance, with high absorption speed and large absorption capacity over a wide viscosity range. This approach has general applicability and can be used to tailor a wide variety of engineering plastic-based aligned porous foams, as long as they can dissolve in organic solvents.

[Reconstruction of anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon in the treatment of chronic lateral ankle instability].

OBJECTIVE: To explore the clinical efficacy of reconstruction the anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon for the treatment of chronic lateral ankle instability. METHODS: The clinical data of 42 patients with chronic lateral ankle instability treated by anatomical reconstruction of anterior talofibular ligament and calcaneofibular ligament with autologous peroneus brevis tendon from July 2016 to July 2019 was retrospectively analyzed. Including 30 males and 12 females, age ranged from 25 to 46 years old with an average of (37.6±12.4) years. There were 15 cases of left foot and 27 cases of right foot, the time from injury to operation was 3 to 12 months with a mean of (7.4±2.8) months. And 14 patients had tenderness in lateral collateral ligament area, 28 patients complained of multiple ankle sprains while walking on the flat ground. At 12 months after operation, the talar tilt angle and visual analogue scale(VAS)were observed, ankle joint varus stress and anterior drawer test were performed to check the mechanical stability of the ankle joint, American Orhopaedic Foot and Ankle Society(AOFAS) was used to score the ankle and hindfoot functions and evaluate the curative effect. RESULTS: Forty patients were followed up for 12 to 48 months with an average of (28.3±10.0) months, 2 cases were lost. The VAS decreased from(4.50±0.93) scores before surgery to (1.10±0.30) scores at 12 months after surgery;the talar tilt angle was reduced from (12.26±1.13)° before operation to (4.60±0.45)° at 12 months after operation;the AOFAS score increased from (65.10±7.50)scores before surgery to (84.40±3.95) scores at 12 months after surgery;all the differences were statically significant(P<0.05). According to the AOFAS score, 27 cases got excellent results, 7 good, 5 fair, and 1 poor. One patient had the symptoms of sural nerve injury after operation, and the symptoms were relieved after oral Mecobalamin for 3 months. The remaining patients had no complications such as nerve injury, infection, and skin necrosis. There was no instability of ankle joint, and both ankle varus stress test and drawer test were negative. CONCLUSION: Autologous peroneal brevis tendon with double bone channel pass through the tendon (modified Chrisman-Snook operation) can anatomically reconstruct the anterior talofibular ligament and the calcaneofibular ligament, restore the stability of the patient's ankle joint, reduce postoperative complications, and restore ankle joint function well.

Identification and Characterization of the Roles of circCASP9 in Gastric Cancer Based on a circRNA-miRNA-mRNA Regulatory Network.

Accumulating evidence demonstrates that circular RNAs (circRNAs) have substantial effects on gastric cancer (GC) tumorigenesis and development. In this study, we performed a screen and identified two differentially expressed circRNAs (circCASP9 and circDLG5) from our circRNA microarray. We validated the expression of circCASP9 and circDLG5 in GC tissues and their normal counterparts by using qRT-PCR. Only circCASP9 was revealed to be downregulated in tumor tissues compared with adjacent normal tissues. Functionally, circCASP9 significantly inhibited the proliferation, migration, and invasion of GC cells both in vitro and in vivo. A competing endogenous RNA (ceRNA) network was constructed for the identification of candidate target genes of circCASP9. circCASP9, two miRNAs, and 55 mRNAs were selected for construction of the ceRNA network. We confirmed that circCASP9 can function as a sponge of miR-589-5p to regulate KANK1 expression, thereby controlling GC progression. Accordingly, we identified that the novel circRNA circCASP9 was differentially expressed between GC tissues and their normal counterparts. We also showed that circCASP9 can regulate the growth and metastasis of GC via the miR-589-5p/KANK1 axis. The circCASP9/miR-589-5p/KANK1 axis might provide crucial insights for investigating the occurrence and development of GC.

Engineered bioresponsive nanotherapeutics: recent advances in the treatment of atherosclerosis and ischemic-related disease.

Biological stimuli that are present during the pathogenesis of disease have gained considerable interest as a critical element for the design of smart drug delivery systems. Recently, the utilization of biological stimuli-responsive (bioresponsive) nanotheranostic agents to treat atherosclerosis and ischemic-related diseases has demonstrated significant outcomes in preclinical studies. Those diseases share similar hallmarks, including high levels of endogenous reactive oxygen species (ROS), low pH, and high enzyme activity. Interestingly, other relevant biological stimuli such as shear stress, cholesterol, and glutathione have recently been explored as internal stimuli to trigger drug release and some particular actions. In addition, a number of strategies can be proposed to enhance their targeting efficiency, diagnostic properties, and efficacy rate. This review discusses recent advancements in the preclinical studies of bioresponsive nanotherapeutics as diagnostic and therapeutic agents against atherosclerosis and ischemic-related diseases as well as some potential strategies to overcome the current limitations.

Lung adenocarcinoma patients have higher risk of SARS-CoV-2 infection.

Both lung adenocarcinoma and coronavirus disease 2019 would cause pulmonary inflammation. Angiotensin-converting enzyme 2, the functional receptor of SARS-CoV-2, also plays a key role in lung adenocarcinoma. To study the risk of SARS-CoV-2 infection in lung adenocarcinoma patients, mRNA and microRNA profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus followed by bioinformatics analysis. A network which regards angiotensin-converting enzyme 2 as the center was structured. In addition, via immunological analysis to explore the essential mechanism of SARS-CoV-2 susceptibility in lung adenocarcinoma. Compared with normal tissue, angiotensin-converting enzyme 2 was increased in lung adenocarcinoma patients. Furthermore, a total of 7 correlated differently expressed mRNAs (ACE2, CXCL9, MMP12, IL6, AZU1, FCN3, HYAL1 and IRAK3) and 5 correlated differently expressed microRNAs (miR-125b-5p, miR-9-5p, miR-130b-5p, miR-381-3p and miR-421) were screened. Interestingly, the most frequent toll-like receptor signaling pathway was enriched by mRNA (interlukin 6) and miRNA (miR-125b-5p) sets simultaneously. In conclusion, it was assumed that miR-125b-5p-ACE2-IL6 axis could alter the risk of SARS-CoV-2 infection in lung adenocarcinoma patients.

UVA-Triggered Drug Release and Photo-Protection of Skin.

Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due to its intrinsic features of being spatially and temporally tunable. Ultraviolet A (UVA) radiation has recently been used as a source of external light stimuli to control the release of drugs using a "switch on- switch off" procedure. This review discusses the promising potential of UVA radiation as the light source of choice for photo-controlled drug release from a range of photo-responsive and photolabile nanostructures via photo-isomerization, photo-cleavage, photo-crosslinking, and photo-induced rearrangement. In addition to its clinical use, we will also provide here an overview of the recent UVA-responsive drug release approaches that are developed for phototherapy and skin photoprotection.