Intelligent Gesture Recognition Based on Screen Reflectance Multi-Band Spectral Features.

Human-computer interaction (HCI) with screens through gestures is a pivotal method amidst the digitalization trend. In this work, a gesture recognition method is proposed that combines multi-band spectral features with spatial characteristics of screen-reflected light. Based on the method, a red-green-blue (RGB) three-channel spectral gesture recognition system has been developed, composed of a display screen integrated with narrowband spectral receivers as the hardware setup. During system operation, emitted light from the screen is reflected by gestures and received by the narrowband spectral receivers. These receivers at various locations are tasked with capturing multiple narrowband spectra and converting them into light-intensity series. The availability of multi-narrowband spectral data integrates multidimensional features from frequency and spatial domains, enhancing classification capabilities. Based on the RGB three-channel spectral features, this work formulates an RGB multi-channel convolutional neural network long short-term memory (CNN-LSTM) gesture recognition model. It achieves accuracies of 99.93% in darkness and 99.89% in illuminated conditions. This indicates the system's capability for stable operation across different lighting conditions and accurate interaction. The intelligent gesture recognition method can be widely applied for interactive purposes on various screens such as computers and mobile phones, facilitating more convenient and precise HCI.

Femtogram-Sensitive Cantilever Platform for Dynamic Graphene Oxide Nanosheet Monitoring.

This study introduces a new approach to optimizing graphene oxide (GO) properties using liquid-phase plasma treatment in a microenvironment. Our innovation exploits atomic force microscopy (AFM) cantilever frequency tracking to monitor mass variations in GO, which are indicative of surface oxidation-reduction processes or substituent doping (boron/nitrogen). Complementary in situ Raman spectroscopy has observed D/G band shifts, and X-ray photoelectron spectroscopy (XPS) determined the C/O ratio and B/N doping levels pre- and post-treatment, confirming chemical tuning to GO. We can achieve femtogram-level precision in detecting nanomaterial mass changes by correlating elemental ratios with AFM cantilever frequency measurements. This multifaceted approach not only enhances our understanding of the chemical properties of GO but also establishes a new, versatile method for monitoring, modifying, and optimizing the properties of nanomaterials.

The Association Between Frailty Evaluated by Clinical Frailty Scale and Mortality of Older Patients in the Emergency Department: A Prospective Cohort Study.

Background: Frailty epitomizes the most complex consequence of an aging population. This study aimed to evaluate the impact of frailty, measured using the Clinical Frailty Scale (CFS), on outcomes of older people in an emergency department (ED). Methods: We conducted a prospective observational study enrolling patients aged 65 years and older in a medical center of Taiwan between March 8, 2021, and November 30, 2021. The primary outcome was 90-day mortality rate. Individuals were categorized into three groups based on the CFS scores. Logistic regression was employed to examine the influence of frailty on clinical outcomes following covariate adjustment. Survival analysis was conducted using Kaplan-Meier curves and Log rank tests. Results: A total of 473 individuals were included in the study, with a mean age of 82.1 years, and 60.5% of them were males. The 90-day mortality rate was 10.6%. Among these groups, the CFS score 7-9 group had the highest 90-day mortality rate (15.9%), followed by the CFS score 4-6 group (8.0%) and the CFS score 1-3 group (7.1%). The multiple logistic regression analyses demonstrated a significant impact of CFS score on prognosis, with adjusted odd ratios of 1.24 (95% CI 1.06-1.47) for 90-day mortality, 1.18 (95% CI 1.06-1.31) for hospitalization, and 1.30 (95% CI 1.12-1.52) for 180-day mortality. The Kaplan-Meier curves revealed a significantly higher 90-day mortality rate for patients with high CFS scores (Log rank tests, p = 0.019). Conclusion: In the older ED population, the severity of frailty assessed by the CFS emerged as a significant and important prognostic factor for hospitalization, 90-day mortality, and 180-day mortality.

Correlates of the Veterans Visiting Emergency Departments in Taiwan: A Comparison Before and After the Coronavirus Disease 2019 Pandemic.

BACKGROUND: Taiwan has a substantial number of veterans, but knowledge regarding their emergency department (ED) visits during the coronavirus disease 2019 (COVID-19) pandemic remains limited. This study examined the characteristics of veterans' ED visits during Taiwan's COVID-19 epidemic. METHODS: This was a cross-sectional study conducted at the ED of a large veteran medical center located in Taipei, Taiwan, from May 2018 to October 2021. We analyzed the numbers and features of visits in summer and autumn according to the first wave of the COVID-19 epidemic in Taiwan in 2021. RESULTS: Medical institutions were positively associated with veteran status. Emergency department complaints of trauma (adjusted odds ratio [AOR] = 1.15, 95% CI: 1.06-1.25; summer P < .01) and chest pain/tightness (AOR = 1.65, 95% CI: 1.45-1.87; summer P < .01; AOR = 1.4, 95% CI: 1.26-1.55; P < .01) were associated with increased odds of being a veteran. Triage levels above 2 were positively associated with veteran status in the autumn model (AOR = 1.14, 95% CI: 1.07-1.22; P < .01). Patients hospitalized after ED visits were associated with reduced odds of veteran status (P < .01). Those who spent a long time in the ED were more likely to be veterans than those who spent a shorter time in the ED (P < .01). Veterans were less likely to visit the ED regardless of the time frame of the study period (P < .01), except during the COVID-19 outbreak in the autumn (2019-2020). CONCLUSIONS: The distinctions in ED visits highlighted the individuality of veterans' medical needs. Our findings suggest that the veteran medical system can add to the focus on improving senior-friendly care, fall prevention, quality of life of institutionalized veterans, access for homeless veterans, and care for ambulatory care-sensitive conditions.

Understanding Healthcare Providers' Care for Patients with Medications Treating Opioid Use Disorder in the Emergency Department: A Scoping Review.

BACKGROUND: There is limited research exploring the changing clinical practices among healthcare providers (HPs) care for patients with Emergency Department (ED)-initiated Medication for Opioid Use Disorder (MOUD). METHODS: This scoping review followed the methodological framework of Arksey and O'Malley to map relevant evidence and synthesize the findings. We searched PubMed, EMBASE, CINAHL, Web of Science, and Scopus for related studies from inception through October 12, 2022. Following the application of inclusion and exclusion criteria, 16 studies were included. Subsequently, they were charted and analyzed thematically based on ecological systems theory. RESULTS: The main determinants in the four ecological systems were generated as follows: (1) microsystem: willingness and attitude, professional competence, readiness, and preference; (2) mesosystem: ED clinical practices, departmental factors; (3) exosystem: multidisciplinary approaches, discharge planning, and (4) macrosystem: stigma, health insurance, policy. The findings have implications for HPs and researchers, as insufficient adoption, implementation, and retention of MOUD in the ED affect clinical practices. CONCLUSIONS: Across the four ecological systems, ED-initiated MOUD is shaped by multifaceted determinants. The microsystem underscores pivotal patient-HP trust dynamics, while the mesosystem emphasizes interdepartmental synergies. Exosystemically, resource allocation and standardized training remain paramount. The macrosystem reveals profound effects of stigma, insurance disparities, and evolving policies on treatment access and efficacy. Addressing these interconnected barriers is crucial for optimizing patient outcomes in the context of MOUD.

Assessing the contribution of semiconductors to the sustainable development goals (SDGs) from 2017 to 2022.

Semiconductor development is a major driving force for global economic growth. However, synchronizing it with the Sustainable Development Goals (SDGs) set by the United Nations remains a critical challenge. To gain insight into this, we analyzed SDG-related publications on semiconductors from 2017 to 2022 using the SciVal database. The study found 77,706 documents related to SDGs in the field of semiconductor research, with an overall increase in the number of publications each year. The main focus of these publications was SDG 7 (Affordable and Clean Energy), accounting for 68.9 % of the total publication count. Additionally, the results indicate that semiconductors have multifaceted potential in advancing a range of SDGs. From fostering innovations in healthcare (SDG 3), ensuring clean water access (SDG 6), catalyzing transformative industrial growth (SDG 9), to contributing to climate mitigation strategies (SDG 13), semiconductors emerge as versatile drivers of sustainable development. The respective publication percentages for these goals were 7.3 %, 5.9 %, 9.7 %, and 4.4 %, underscoring their capacity to make substantial contributions across various facets of sustainability. It's worth noting that only 2.9 % of these publications stem from academia-industry collaborations. This indicates a pressing need to facilitate collaboration between academia and industry, as such partnerships have the potential to amplify the impact of semiconductor innovations on the SDGs. The novelty of this study lies in its specific exploration through a comprehensive analysis spanning five years, revealing the alignment between semiconductor advancements and the latest SDGs. It uncovers the significance of collaborative ecosystems involving research institutions, businesses, and governments. Through these results, our study addresses a gap in the existing literature and advances semiconductor contributions to the SDGs.

Woman With Hematochezia.

As a consequence of cirrhosis, portal hypertension causes resistance to blood flow and leads to the formation of varices. However, colonic variceal hemorrhages are rarely reported but could be a lethal cause of lower gastrointestinal hemorrhage. Currently, there is no consensus on the management of colonic variceal hemorrhage. Variceal ligation, injection sclerotherapy, transjugular intrahepatic portosystemic shunt placement, and balloon-occluded retrograde transvenous obliteration or a combination of the above therapies have been reported with inconsistent success rates. We advocate considering colonic variceal bleeding as a crucial differential diagnosis of lower gastrointestinal bleeding in cirrhotic patients and initiating time-sensitive, definite operative treatment or combination therapy as soon as possible in colonic variceal patients with life-threatening bleeding events, which are often refractory to conservative treatment.

The impact of COVID-19 epidemic on emergency department visits of older patients in Taiwan.

BACKGROUND: The number of emergency department (ED) visits has significantly declined since the COVID-19 pandemic. In Taiwan, an aged society, it is unknown whether older adults are accessing emergency care during the COVID-19 epidemic. Therefore, this study aimed to investigate the impact of COVID-19 on the ED visits and triage, admission, and intensive care unit (ICU) hospitalization of the geriatric population in a COVID-19-dedicated medical center throughout various periods of the epidemic. METHODS: A retrospective chart review of ED medical records from April 9 to August 31, 2021 were conducted, and demographic information was obtained from the hospital's computer database. The period was divided into pre-, early-, peak-, late-, and post-epidemic stages. For statistical analysis, one-way analysis of variance followed by multiple comparison tests (Bonferroni correction) were used. RESULTS: A statistically significant decrease in the total number of patients attending the ED was noted during the peak-, late-, and post-epidemic stages. In the post-epidemic stage, the number of older patients visiting ED was nearly to that of the pre-epidemic stage, indicating that older adults tend to seek care at the ED earlier than the general population. Throughout the entire epidemic period, there was no statistically significant reduction in the number of the triage 1& 2 patients seeking medical attention at the emergency department. In the entire duration of the epidemic, there was no observed reduction in the admission of elderly patients to our hospital or ICU through the ED. However, a statistically significant decrease was observed in the admission of the general population during the peak epidemic stage. CONCLUSIONS: During the peak of COVID-19 outbreak, the number of ED visits was significantly affected. However, it is noteworthy that as the epidemic was gradually controlled, the older patients resumed their ED visits earlier that the general population as indicated by the surge in their number. Additionally, in the patient group of triage 1& 2, which represents a true emergency, the number did not show a drastic change.

Contrast-enhanced ultrasound-guided biopsy of suspicious breast lesions on contrast-enhanced mammography and contrast-enhanced MRI: a case series.

PURPOSE: To assess the effectiveness of contrast-enhanced ultrasound (CEUS) in guiding biopsies of breast lesions that were detected on contrast-enhanced mammography (CEM) or contrast-enhanced breast MRI (CE-MRI) but were not clearly visible on B-mode ultrasound (B-US). METHODS: In this study, 23 lesions in 16 patients were selected for CEUS-guided biopsy due to poor visualization on B-US despite being detected on CEM (n = 20) or CE-MRI (n = 3). B-US, color Doppler ultrasound (CDUS), and CEUS were used to visualize the suspicious lesions, followed by a CEUS-guided core needle biopsy using Sonazoid as the contrast agent. The accuracy of the biopsy was assessed based on pathology-radiology concordance and 12-month imaging follow-up. The conspicuity scores for lesion visualization were evaluated using a 5-point conspicuity scale agreed upon by two breast radiologists. RESULTS: The enhancing lesions detected on CEM/CE-MRI had an average size of 1.6 ± 1.3 cm and appeared as mass-enhancing (61%) or non-mass-enhancing (39%). The lesions had mean conspicuity scores of 2.30 on B-US, 2.78 on CDUS, and 4.61 on CEUS, with 96% of the lesions showing contrast enhancement on CEUS. CEUS-guided biopsy showed increased visibility in 96% and 91% of the lesions compared to B-US and CDUS, respectively. The overall accuracy of CEUS-guided biopsy was 100% based on concordance with histology and 12-month follow-up. CONCLUSIONS: CEUS enhances the visibility of suspicious CEM/CE-MRI lesions that are poorly visible on B-US during biopsy procedures.

Rapid identification and detection of aristolochic acids in the herbal extracts by Raman spectroscopy.

Herbs containing aristolochic acids (AAs) have already been proven to be highly carcinogenic and nephrotoxic. In this study, a novel surface-enhanced Raman scattering (SERS) identification method was developed. Ag-APS nanoparticles with a particle size of 3.53 ± 0.92 nm were produced by combining silver nitrate and 3-aminopropylsilatrane. The reaction between the carboxylic acid group of aristolochic acid I (AAI) and amine group of Ag-APS NPs was used to form amide bonds, and thus, concentrate AAI, rendering it easy to detect via SERS and amplified to obtain the best SERS enhancement effect. Detection limit was calculated to be approximately 40 nM. Using the SERS method, AAI was successfully detected in the samples of four Chinese herbal medicines containing AAI. Therefore, this method has a high potential to be applied in the future development of AAI analysis and rapid qualitative and quantitative analysis of AAI in dietary supplements and edible herbs.

BiTE-Secreting CAR-γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors.

HLA-G is considered as an immune checkpoint protein and a tumor-associated antigen. In the previous work, it is reported that CAR-NK targeting of HLA-G can be used to treat certain solid tumors. However, the frequent co-expression of PD-L1 and HLA-G) and up-regulation of PD-L1 after adoptive immunotherapy may decrease the effectiveness of HLA-G-CAR. Therefore, simultaneous targeting of HLA-G and PD-L1 by multi-specific CAR could represent an appropriate solution. Furthermore, gamma-delta T (γδT) cells exhibit MHC-independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA-driven, nanobody-based HLA-G-CAR with a secreted PD-L1/CD3ε Bispecific T-cell engager (BiTE) construct (Nb-CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb-CAR.BiTE-γδT cells could effectively eliminate PD-L1 and/or HLA-G-positive solid tumors. The secreted PD-L1/CD3ε Nb-BiTE can not only redirect Nb-CAR-γδT but also recruit un-transduced bystander T cells against tumor cells expressing PD-L1, thereby enhancing the activity of Nb-CAR-γδT therapy. Furthermore, evidence is provided that Nb-CAR.BiTE redirectes γδT into tumor-implanted tissues and that the secreted Nb-BiTE is restricted to the tumor site without apparent toxicity.

Taiwan's National Health Insurance at the Emergency Department following the COVID-19 outbreak.

Taiwan's National Health Insurance (NHI) is a widely acclaimed universal healthcare system. In the past few years, particularly following the COVID-19 outbreak, challenges related to maintaining the NHI system have surfaced. Since 2020, NHI has faced a series of challenges, including excessive patient visits to the hospital emergency department, a lack of an effective primary care and referral system, and a high turnover rate of healthcare workers. We review major problems related to Taiwan's NHI, emphasizing input from frontline healthcare workers. We provide recommendations for potential policies addressing the concerns around NHI, for example, strengthening the role of primary care services under the NHI administration, reducing the high turnover rate of healthcare workers, and increase the premium and copayments. We hope that this policy analysis may allow policymakers and scholars to understand both the merits and critical problems related to NHI from the clinical perspective.

Syllable or phoneme? A mouse-tracking investigation of phonological units in Mandarin Chinese and English spoken word recognition.

Previous studies on spoken word production have shown that native English speakers used phoneme-sized units (e.g., a word-initial phoneme, C) to produce English words, and native Mandarin Chinese speakers employed syllable-sized units (e.g., a word-initial consonant and vowel, CV) as phonological encoding units in Chinese. With spoken word production, although spoken word recognition is a fundamental language skill of human beings, it is unknown whether a Chinese-English bilingual listener can adjust the phonological unit sizes depending on the language used. Using four mouse-tracking spoken word recognition experiments, participants listened to spoken words (either presented in English or Chinese) while viewing a display of two written words. In Experiment 1, Chinese-English bilinguals experienced a larger phonological competition in the CV condition than the control condition, indicating that they recruited syllables when listening to Chinese monosyllabic words. Experiment 2 extended the results of Experiment 1 with a set of Chinese disyllabic words and further revealed the temporal distribution of syllable overlap of a spoken word constrains phonological competition. In Experiment 3, Chinese-English bilinguals exhibited a greater phonological competition in both CV and C conditions that mirrored those reported with English monolinguals in Experiment 4. Our results across experiments demonstrated that Chinese-English bilinguals employed both phonemes and syllables to recognize English spoken words but exclusively relied on syllables to recognize Chinese words, suggesting that there is flexibility in selecting phonological units when recognizing spoken words in the two languages. Implications for models of monolingual and bilingual spoken recognition are also discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

SRT1720 as an SIRT1 activator for alleviating paraquat-induced models of Parkinson's disease.

Epidemiological studies have linked herbicides and Parkinson's disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1 synthesized by Sirtris, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720's protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1α and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD.

Hand gestures recognition in videos taken with a lensless camera.

A lensless camera is an imaging system that uses a mask in place of a lens, making it thinner, lighter, and less expensive than a lensed camera. However, additional complex computation and time are required for image reconstruction. This work proposes a deep learning model named Raw3dNet that recognizes hand gestures directly on raw videos captured by a lensless camera without the need for image restoration. In addition to conserving computational resources, the reconstruction-free method provides privacy protection. Raw3dNet is a novel end-to-end deep neural network model for the recognition of hand gestures in lensless imaging systems. It is created specifically for raw video captured by a lensless camera and has the ability to properly extract and combine temporal and spatial features. The network is composed of two stages: 1. spatial feature extractor (SFE), which enhances the spatial features of each frame prior to temporal convolution; 2. 3D-ResNet, which implements spatial and temporal convolution of video streams. The proposed model achieves 98.59% accuracy on the Cambridge Hand Gesture dataset in the lensless optical experiment, which is comparable to the lensed-camera result. Additionally, the feasibility of physical object recognition is assessed. Further, we show that the recognition can be achieved with respectable accuracy using only a tiny portion of the original raw data, indicating the potential for reducing data traffic in cloud computing scenarios.

Text detection and recognition based on a lensless imaging system.

Lensless cameras are characterized by several advantages (e.g., miniaturization, ease of manufacture, and low cost) as compared with conventional cameras. However, they have not been extensively employed due to their poor image clarity and low image resolution, especially for tasks that have high requirements on image quality and details such as text detection and text recognition. To address the problem, a framework of deep-learning-based pipeline structure was built to recognize text with three steps from raw data captured by employing lensless cameras. This pipeline structure consisted of the lensless imaging model U-Net, the text detection model connectionist text proposal network (CTPN), and the text recognition model convolutional recurrent neural network (CRNN). Compared with the method focusing only on image reconstruction, U-Net in the pipeline was able to supplement the imaging details by enhancing factors related to character categories in the reconstruction process, so the textual information can be more effectively detected and recognized by CTPN and CRNN with fewer artifacts and high-clarity reconstructed lensless images. By performing experiments on datasets of different complexities, the applicability to text detection and recognition on lensless cameras was verified. This study reasonably demonstrates text detection and recognition tasks in the lensless camera system, and develops a basic method for novel applications.

Comprehensive Geriatric Assessment in the Emergency Department for Identifying Elderly Individuals at Risk of Hip Fracture.

Background: Hip fracture (HF) is a major challenge for healthcare systems in terms of increased costs and lengths of stay, and it has been estimated that by 2050, half of the projected 6.26 million global HFs will occur in Asia. Owing to the high morbidity and mortality associated with HF in elderly individuals, it is crucial to recognize at-risk elderly patients in the ED so that special precautions and preventive measures can be taken. While comprehensive geriatric assessment (CGA) has been shown to improve outcomes and prevent secondary fractures in elderly individuals with HF in outpatient settings, there is a lack of data to identify elderly Asian patients who are at risk of HF via using CGA in the emergency department (ED). The aim of this study is to identify the characteristics of elderly Asian patients in the ED who have an increased risk of HF via CGA. Methods: A case-control study was conducted in the ED at Taipei Veterans General Hospital, a medical center located in Taipei, Taiwan, from October 2018 to December 2019. Patients > 75 years old with and without HF were compared using data obtained from CGAs conducted by trained nurses. Results: A total of 85 HF patients (cases) and 680 non-HF patients were enrolled, among whom 340 non-HF control individuals (controls) were selected by simple random sampling. HF occurred more frequently in women and in patients with depressive symptoms. An association between decreased handgrip strength and HF risk, especially in men, was also identified ( p = 0.011). The variables independently associated with the presence of HF in the multivariate analysis were female sex (odds ratio [OR]: 2.229; 95% confidence interval [CI]: 1.332-3.728) and decreased handgrip strength (OR: 2.462; 95% CI: 1.155-5.247). Conclusions: By performing CGAs in the ED, we found that female sex and decreased handgrip strength were associated with HF risk. Therefore, we propose that targeted assessment of handgrip strength in female patients aged > 75 years in the ED may identify those at greatest risk of HF, resulting in improved emergency care for geriatric patients.

Optically switched multiband antenna based on Vivaldi structure.

In this study, an optically frequency-reconfigurable antenna with multiband characteristics is proposed utilizing photodiodes. It is developed on the basis of a Vivaldi antenna structure, while the composite radiation structure is realized by introducing three parallel branches in the antenna slot. Three photodiodes on the branches function as photoconductive switches to make the antenna reconfigurable at multiple low frequencies and stable at high frequencies. When the illumination irradiates different photodiodes, the proposed antenna is capable to switch between three narrowband modes, including 300 MHz, 677 MHz, and 1.02 GHz. The radiation gain is measured to reach 0.91 dB, 1.69 dB, 2.96 dB, respectively, while the variation in illumination states is 6.82 dB, 9.93 dB, 17.13 dB, respectively. Meanwhile, this antenna can continue to work stably at 3.2-3.8 GHz and 5.1-6.5 GHz regardless of illumination, with the maximum gain of 7.51 dB. Both simulation and experimental results substantiate the feasibility of the proposed design. This antenna design can transmit and shield the signal of specific frequency with optical control, and has good working characteristics at both high and low frequencies. In the future, it has promising application potential of communication and radar integration.

Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells.

BACKGROUND: Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells. OBJECTIVE: To determine whether lysosomes are involved in IMQ-induced apoptosis. METHODS: The human skin cancer cell lines BCC, A375 and mouse melanoma cell line B16F10 were used in all experiments. Cell death was determined by the Cell Counting Kit-8 (CCK-8) assay and DNA content assay. Protein expression was determined by immunoblotting. Caspase-8 activity was assessed using a fluorescence caspase-8 kit and determined by flow cytometry and confocal microscopy. RESULTS: IMQ not only induced lysosome damage but also abrogated lysosome function in skin cancer cells. IMQ-induced caspase-8 activation contributed to the processes of lysosomal cell death. Moreover, the use of ROS scavengers significantly abolished caspase-8 activation and inhibited IMQ-induced LMP. Additionally, pharmacological inhibition of CTSD not only abrogated caspase-8 activation but also rescued IMQ-induced cell death. Finally, lysosome-alkalizing agents enhanced the cytotoxicity of IMQ in vitro and in vivo. CONCLUSIONS: IMQ-induced ROS accumulation promotes LMP, releases CTSs into the cytosol, stimulates caspase-8 activation and finally causes lysosomal cell death. Lysosomal cell death and the CTSD/caspase-8 axis may play a crucial role in IMQ-induced cell death.

Discussion on several statistical problems in establishing quality standards of standard decoctions.

Since 2016, a number of studies have been published on standard decoctions used in Chinese medicine. However, there is little research on statistical issues related to establishing the quality standards for standard decoctions. In view of the currently established quality standard methods for standard decoctions, an improvement scheme is proposed from a statistical perspective. This review explores the requirements for dry matter yield rate data and index component transfer data for the application of two methods specified in "Technical Requirements for Quality Control and Standard Establishment of Chinese Medicine Formula Granules," which include the average value plus or minus three times the standard deviation ( X - ± 3 S D ) or 70% to 130% of the average value ( X - ± 30 % X - ). The square-root arcsine transformation method is used as an approach to solve the problem of unreasonable standard ranges of standard decoctions. This review also proposes the use of merged data to establish a standard. A method to judge whether multiple sets of standard decoction data can be merged is also provided. When multiple sets of data have a similar central tendency and a similar discrete tendency, they can be merged to establish a more reliable quality standard. Assuming that the dry matter yield rate and transfer rate conform to a binomial distribution, the number of batches of prepared slices that are needed to establish the standard decoction quality standard is estimated. It is recommended that no less than 30 batches of prepared slices should be used for the establishment of standard decoction quality standards.