SIRT1: An Intermediator of Key Pathways Regulating Pulmonary Diseases.

Silent information regulator type-1 (SIRT1), a nicotinamide adenine dinucleotide+-dependent deacetylase, is a member of the sirtuins family and has unique protein deacetylase activity. SIRT1 participates in physiological as well as pathophysiological processes by targeting a wide range of protein substrates and signalings. In this review, we described the latest progress of SIRT1 in pulmonary diseases. We have introduced the basic information and summarized the prominent role of SIRT1 in several lung diseases, such as acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, lung cancer, and aging-related diseases.

Variational autoencoder-assisted unsupervised hardware fingerprint authentication in a fiber network.

Physical-layer authentication (PLA) based on hardware fingerprints can safeguard optical networks against large-scale masquerade or active injection attacks. However, traditional schemes rely on massive labeled close-set data. Here, we propose an unsupervised hardware fingerprint authentication based on a variational autoencoder (VAE). Specifically, the triplets are generated through variational inference on unlabeled optical spectra and then applied to train the feature extractor, which has an excellent generalization ability and enables fingerprint feature extraction from previously unknown optical transmitters. The feasibility of the proposed scheme is experimentally verified by the successful classification of eight optical transmitters after a 20 km standard single-mode fiber (SSMF) transmission, to distinguish efficiently the rogue from legal devices. A recognition accuracy of 99% and a miss alarm rate of 0% are achieved even under the interference of multiple rogue devices. Moreover, the proposed scheme is verified to have a comparable performance with the results obtained from supervised learning.

A 300†km fiber channel mapping using neural networks for Gb/s physical-layer key distribution.

Physical-layer secure key distribution (PLSKD) generally acquires highly correlated entropy sources via bidirectional transmission to share the channel reciprocity. For long-haul fiber links, the non-negligible backscattering noise (BSN) and the challenge of bidirectional optical amplification degrade the key generation performances. Since the channel reciprocity can be precisely mapped using neural networks (NNs), unidirectional PLSKD provides a feasible PLSKD for longer fiber links. Here, a final error-free key generation rate (KGR) in unidirectional PLSKD of 3.07 Gb/s is demonstrated over a 300 km fiber link using NNs. Moreover, the channel mapping is analyzed in terms of fiber distance, chromatic dispersion, the nonlinearity of random source, and BSN.

Downregulation of ALKBH5 rejuvenates aged human mesenchymal stem cells and enhances their therapeutic efficacy in myocardial infarction.

Despite promising results in myocardial infarction (MI), mesenchymal stem cell (MSC)-based therapy is limited by cell senescence. N6-methyladenosine (m6A) messenger RNA methylation has been reported to be closely associated with cell senescence. Nonetheless, its role in the regulation of MSC senescence remains unclear. We examined the role of ALKB homolog 5 (ALKBH5) in regulating MSC senescence and determined whether ALKBH5 downregulation could rejuvenate aged MSCs (AMSCs) to improve their therapeutic efficacy for MI. RNA methylation was determined by m6A dot blotting assay. MSC senescence was evaluated by senescence-associated ß-galactosidase (SA-ß-gal) staining. A mouse model of acute MI was established by ligation of the left anterior decedent coronary artery (LAD). Compared with young MSCs (YMSCs), m6A level was significantly reduced but ALKBH5 was greatly increased in AMSCs. Overexpression of ALKBH5 reduced m6A modification and accelerated YMSC senescence. Conversely, ALKBH5 knockdown increased m6A modifications and alleviated AMSC senescence. Mechanistically, ALKBH5 regulated the m6A modification and stability of CDKN1C mRNA, which further upregulated CDKN1C expression, leading to MSC senescence. CDKN1C overexpression ameliorated the inhibition of cellular senescence of ALKBH5 siRNA-treated AMSCs. More importantly, compared with AMSCs, shALKBH5-AMSCs transplantation provided a superior cardioprotective effect against MI in mice by improving MSC survival and angiogenesis. We determined that ALKBH5 accelerated MSC senescence through m6A modification-dependent stabilization of the CDKN1C transcript, providing a potential target for MSC rejuvenation. ALKBH5 knockdown rejuvenated AMSCs and enhanced cardiac function when transplanted into the mouse heart following infarction.

Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.

Doxorubicin (DOX) is a chemotherapeutic agent widely used for tumor treatment. Nonetheless its clinical application is heavily limited by its cardiotoxicity. There is accumulated evidence that transplantation of mesenchymal stem cell-derived exosomes (MSC-EXOs) can protect against Dox-induced cardiomyopathy (DIC). This study aimed to examine the cardioprotective effects of EXOs isolated from human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) against DIC and explore the potential mechanisms. EXOs were isolated from the cultural supernatant of human BM-MSCs (BM-MSC-EXOs) and iPSC-MSCs (iPSC-MSC-EXOs) by ultracentrifugation. A mouse model of DIC was induced by intraperitoneal injection of Dox followed by tail vein injection of PBS, BM-MSC-EXOs, or iPSC-MSC-EXOs. Cardiac function, cardiomyocyte senescence and mitochondrial dynamics in each group were assessed. In vitro, neonatal mouse cardiomyocytes (NMCMs) were subjected to Dox and treated with BM-MSC-EXOs or iPSC-MSC-EXOs. The mitochondrial morphology and cellular senescence of NMCMs were examined by Mitotracker staining and senescence-associated-ß-galactosidase assay, respectively. Compared with BM-MSC-EXOs, mice treated with iPSC-MSC-EXOs displayed improved cardiac function and decreased cardiomyocyte mitochondrial fragmentation and senescence. In vitro, iPSC-MSC-EXOs were superior to BM-MSC-EXOs in attenuation of cardiomyocyte mitochondrial fragmentation and senescence caused by DOX. MicroRNA sequencing revealed a higher level of miR-9-5p in iPSC-MSC-EXOs than BM-MSC-EXOs. Mechanistically, iPSC-MSC-EXOs transported miR-9-5p into DOX-treated cardiomyocytes, thereby suppressing cardiomyocyte mitochondrial fragmentation and senescence via regulation of the VPO1/ERK signal pathway. These protective effects and cardioprotection against DIC were largely reversed by knockdown of miR-9-5p in iPSC-MSC-EXOs. Our results showed that miR-9-5p transferred by iPSC-MSC-EXOs protected against DIC by alleviating cardiomyocyte senescence via inhibition of the VPO1/ERK pathway. This study offers new insight into the application of iPSC-MSC-EXOs as a novel therapeutic strategy for DIC treatment.

African American patients have a higher probability of cognitive impairment after incident stroke: An analysis of national electronic health record data.

BACKGROUND: Cognitive impairment (CI) and stroke are diseases with significant disparities in race and geography. Post stroke cognitive impairment (PSCI) can be as high as 15-70 % but few studies have utilized large administrative or electronic health records (EHR) to evaluate trends in PSCI. We utilized an EHR database to evaluate for disparities in PSCI in a large sample of patients after first recorded stroke to evaluate for disparities in race. METHODS: This is a retrospective cohort analysis of Cerner Health Facts® EHR database, which is comprised of EHR data from hundreds of hospitals/clinics in the US from 2009-2018. We evaluated patients ≥40 years of age with a first time ischemic stroke (IS) diagnosis for PSCI using ICD9/10 codes for both conditions. Patients with first stroke in the Cerner database and no pre-existing cognitive impairment were included, we compared hazard ratios for developing PSCI for patient characteristics RESULTS: A total of 150,142 IS patients with follow-up data and no pre-existing evidence of CI were evaluated. Traditional risk factors of age, female sex, kidney injury, hypertension, and hyperlipidemia were associated with PSCI. Only African American stroke survivors had a higher probability of developing PSCI compared to White survivors (HR 1.347, 95 % CI (1.270, 1.428)) and this difference was most prominent in the South. Among those to develop PSCI, median time to documentation was 1.8 years in African American survivors. CONCLUSION: In a large national database, African American stroke survivors had a higher probability of PSCI five years after stroke than White survivors.

10 Gb/s physical-layer key distribution in fiber using amplified spontaneous emission.

High-speed physical-layer secure key generation and distribution (SKGD) schemes via channel reciprocity are achieved using external electro-optical modulation or random source distribution via additional fiber links. Here, we propose and demonstrate an SKGD scheme using the fluctuation of polarization states from an amplified spontaneous emission (ASE) source, without any external electro-optical modulation or additional fiber link. Experimentally, an error-free key generation rate (KGR) of 10.1 Gb/s is achieved over a 10-km standard single-mode fiber (SSMF), with true randomness originating from ASE. Moreover, the single fiber channel can be shared for SKGD as well as data transmission, allowing the integration of the proposed SKGD with the deployed fiber infrastructure.

Biological Correlates of the Effects of Auricular Point Acupressure on Pain.

BACKGROUND: To identify candidate inflammatory biomarkers for the underlying mechanism of auricular point acupressure (APA) on pain relief and examine the correlations among pain intensity, interference, and inflammatory biomarkers. DESIGN: This is a secondary data analysis. METHODS: Data on inflammatory biomarkers collected via blood samples and patient self-reported pain intensity and interference from three pilot studies (chronic low back pain, n = 61; arthralgia related to aromatase inhibitors, n = 20; and chemotherapy-induced neuropathy, n = 15) were integrated and analyzed. This paper reports the results based on within-subject treatment effects (change in scores from pre- to post-APA intervention) for each study group (chronic low back pain, cancer pain), between-group differences (changes in scores from pre- to post-intervention between targeted-point APA [T-APA] and non-targeted-point APA [NT-APA]), and correlations among pain intensity, interference, and biomarkers. RESULTS: Within-group analysis (the change score from pre- to post-APA) revealed statistically significant changes in three biomarkers: TNF-α (cancer pain in the APA group, p = .03), ß-endorphin (back pain in the APA group, p = .04), and IL-2 (back pain in the NT-APA group, p = .002). Based on between-group analysis in patients with chronic low back pain (T-APA vs NT-APA), IL-4 had the largest effect size (0.35), followed by TNF-α (0.29). A strong positive monotonic relationship between IL-1ß and IL-2 was detected. CONCLUSIONS: The current findings further support the potential role of inflammatory biomarkers in the analgesic effects of APA. More work is needed to gain a comprehensive understanding of the underlying mechanisms of APA on chronic pain. Because it is simple, inexpensive, and has no negative side effects, APA can be widely disseminated as an alternative to opioids.

Point to multi-point physical-layer key generation and distribution in passive optical networks.

A point to multi-point physical-layer secure key generation and distribution (SKGD) scheme is proposed and demonstrated in passive optical networks (PONs), where the optical line terminal (OLT) broadcasts optical lights with fast fluctuating states of polarization (SOPs) to the optical network units (ONUs). The highly correlated key waveforms are shared between OLT and ONUs, and the high-level security of the SKGD scheme is guaranteed by the high sensitivity of SOP dynamics associated with the specific fiber links. As a proof of concept, a 3.9 Gb/s SKGD is achieved over 11 km single-mode fiber, where a Sagnac interferometer-based polarization scrambler is constructed as the high-speed random source. Moreover, the generated key sequences are verified to be error free and truly random. The proposed SKGD scheme offers a flexible solution for security enhancement in PONs, and is also compatible with the current PON infrastructure.

Retention, adherence, and acceptability testing of a digital health intervention in a 3-group randomized controlled trial for chronic musculoskeletal pain.

OBJECTIVES: Evaluate a digital health intervention using Auricular Point Acupressure (APA) for chronic musculoskeletal pain in terms of participant retention, adherence, acceptability, and satisfaction. Chronic musculoskeletal pain is a global concern and there are persistent challenges in pain management. Despite the value of digital health interventions, these interventions need to be fully evaluated for feasibility. METHODS: We conducted a 3-group, longitudinal, randomized controlled trial (RCT). After Institutional Review Board approval, we posted recruitment flyers in a university, healthcare clinics, and community settings. Participants were randomized into an in-person + app group (n = 8), virtual + app group (n = 7), and a wait-list, education-enhanced control group (n = 8), evaluating our outcomes using standard feasibility measures. The 4-week intervention consisted of virtual sessions, telecommunications, and our APA app, followed by a 3-month follow-up. RESULTS: Data from 22 participants were subsequently analyzed (95.7%). All app participants adhered to the study protocol and used APA at the minimum recommended frequency and duration. The virtual + app group used APA more during the intervention and follow-up periods. All app participants found the intervention to be acceptable and at least 80% overall were satisfied with APA at the 3-month follow-up. There were no adverse events reported. CONCLUSIONS: Our digital health intervention was found to be acceptable and sustainable; participants adhered to and were satisfied with the intervention providing support for a larger RCT. CLINICAL TRIAL: #: NCT05020470.

A20 Promoter rs5029924 Concomitant with rs2230926 and rs5029937 May Be a Prognostic Predictor for Joint Deformity or Refractory Rheumatoid Arthritis.

Background: There have been several studies regarding the susceptibility of A20 gene SNPs (rs2230926 and rs5029937) in rheumatoid arthritis (RA). However, little is known about the association between polymorphisms in the A20 promoter and RA. The aim of this study was to investigate the characteristics of A20 promoter polymorphisms and the association between these polymorphisms and clinical significance in Chinese RA patients. Methods: PCR and sequencing were used to identify A20 gene polymorphisms in peripheral blood mononuclear cells (PBMCs) from 123 RA cases and 31 healthy individuals. Results: Only one SNP (rs5029924) in the A20 gene promoter was identified in RA patients and healthy individuals. 6 patients who carried heterozygous rs5029924 (3918C>T) together with heterozygous rs5029937 (11,571 G>T) and rs2230926 (12,486 T>G, Phe127Cys) suffered from joints deformity or refractory RA. Conclusion: We reported the A20 promoter polymorphism rs5029924 in RA patients for the first time. rs5029924 concomitant with rs2230926 and rs5029937 may be a prognostic predictor for joint deformity or refractory RA.

ALDH2 regulates mesenchymal stem cell senescence via modulation of mitochondrial homeostasis.

Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and aging-related diseases, its role in the regulation of human mesenchymal stem cell (MSC) senescence has not been investigated. This study aimed to determine the role of ALDH2 in regulating MSC senescence and illustrate the potential mechanisms. MSCs were isolated from young (YMSCs) and aged donors (AMSCs). Senescence-associated ß-galactosidase (SA-ß-gal) staining and Western blotting were used to assess MSC senescence. Reactive oxygen species (ROS) generation and mitochondrial membrane potential were determined to evaluate mitochondrial function. We showed that the expression of ALDH2 increased alongside cellular senescence of MSCs. Overexpression of ALDH2 accelerated YMSC senescence whereas down-regulation alleviated premature senescent phenotypes of AMSCs. Transcriptome and biochemical analyses revealed that an elevated ROS level and mitochondrial dysfunction contributed to ALDH2 function in MSC senescence. Using molecular docking, we identified interferon regulatory factor 7 (IRF7) as the potential target of ALDH2. Mechanistically, ectopic expression of ALDH2 led to mitochondrial dysfunction and accelerated senescence of MSCs by increasing the stability of IRF7 through a direct physical interaction. These effects were partially reversed by knockdown of IRF7. These findings highlight a crucial role of ALDH2 in driving MSC senescence by regulating mitochondrial homeostasis, providing a novel potential strategy against human aging-related diseases.

Innovative regression model-based decision support tool for optimizing radiotherapy techniques in thoracic esophageal cancer.

Background: Modern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques. Methods: We enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients. Results: Using predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability. Conclusion: In summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.

TRAF3IP2 drives mesenchymal stem cell senescence via regulation of NAMPT-mediated NAD biosynthesis.

The cellular senescence of mesenchymal stem cells (MSCs) limits their application in regenerative medicine. This study aimed to clarify the role of TNF receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a pro-inflammatory cytoplasmic adaptor protein, in regulating MSC senescence and to explore the potential mechanisms. Methods: MSC senescence was determined by senescence-associated ß-galactosidase (SA-ß-gal) staining. The expression of TRAF3IP2 and senescence-related proteins was detected by Western blotting. The nicotinamide adenine dinucleotide (NAD+) level and nicotinamide phosphoribosyl transferase (NAMPT) expression in MSCs was measured. Results: Compared with that in MSCs isolated from young donors (YMSCs), the expression of TRAF3IP2 was greatly increased in MSCs derived from aged donors (AMSCs). Overexpression of TRAF3IP2 accelerated YMSC senescence whereas downregulation significantly rescued cellular senescence. The protein level of NAMPT and the level of NAD+ were significantly decreased in AMSCs compared with YMSCs. Mechanistically, TRAF3IP2 induced MSC senescence via downregulation of NAMPT expression and NAD + level by inhibiting the AMPK signaling pathway. These effects were partially reversed by treatment with an AMPK or NAMPT activator. Conclusion: We revealed that TRAF3IP2 accelerated MSC senescence via downregulation of NAMPT-mediated NAD biosynthesis by mediation of the AMPK pathway, highlighting a novel means to rejuvenate senescent MSCs.

Nurse-Administered Auricular Point Acupressure for Cancer-Related Pain.

PURPOSE: The study aimed to (1) examine the feasibility of providing a training course on auricular point acupressure (APA) for clinical oncology nurses to integrate APA into real-world nursing care settings, and (2) examine the effectiveness of APA on cancer-related pain (CRP) under usual inpatient oncology ward conditions. METHODS: This was a 2-phase feasibility study. Phase 1, an in-person, 8 hour training program was provided to oncology nurses. Phase 2, a prospective and feasibility study was conducted to evaluate the integration of APA into nursing care activities to manage CRP. Oncology patients were included if their pain was rated at ≥4 on a 0 to 10 numeric rating scale in the past 24 hours. Patients received 1 APA treatment administered by the nurses and were instructed to stimulate the points for 3 days. Study outcomes (pain intensity, fatigue, and sleep disturbance), pain medication use, and APA practice were measured by a phone survey daily. RESULTS: Ten oncology nurses received APA training in phase 1. APA had been added to the hospital's electronic health records (EHRs) as a pain treatment. In phase 2, 33 oncology patients received APA treatment with a 100% adherence rate (pressing the seeds 3 times per day, 3 minutes per time based on the suggestion). The side effects of APA were minimal (~8%-12% felt tenderness on the ear). After 3 days of APA, patients reported 38% pain relief, 39% less fatigue, and 45% improvement in sleep disturbance; 24% reduced any type of pain medication use and 19% reduced opioid use (10 mg opioids using milligram morphine equivalent). The major barrier to integrating APA into routine nursing practice was time management (how to include APA in a daily workflow). CONCLUSION: It is feasible to provide 8-hour training to oncology nurses for mastering APA skill and then integrating APA into their daily nursing care for patients with CRP. Based on the promising findings (decreased pain, improved fatigue and sleep disturbance, and less opioid use), the next step is to conduct a randomized clinical trial with a larger sample to confirm the efficacy of APA for oncology nurses to treat CRP in real-world practice.ClinicalTrial.gov identifier number: NCT04040140.

Does Spasticity Correlate With Motor Impairment in the Upper and Lower Limbs in Ambulatory Chronic Stroke Survivors?

OBJECTIVE: This study aimed to explore correlations between spasticity and motor impairments in the upper and lower limbs in ambulatory chronic stroke survivors. DESIGN: We performed clinical assessments in 28 ambulatory chronic stroke survivors with spastic hemiplegia (female: 12; male: 16; mean ages = 57.8 ± 11.8 yrs; 76 ± 45 mos after stroke). RESULTS: In the upper limb, spasticity index and Fugl-Meyer Motor Assessment showed a significant correlation. Spasticity index for the upper limb showed a significant negative correlation with handgrip strength of the affected side ( r = -0.4, P = 0.035) while Fugl-Meyer Motor Assessment for the upper limb had a significant positive correlation ( r = 0.77, P < 0.001). In the LL, no correlation was found between SI_LL and FMA_LL. There was a significant and high correlation between timed up and go test and gait speed ( r = 0.93, P < 0.001). Gait speed was positively correlated with Spasticity index for the lower limb ( r = 0.48, P = 0.01), and negatively correlated with Fugl-Meyer Motor Assessment for the lower limb ( r = -0.57, P = 0.002). Age and time since stroke showed no association in analyses for both upper limb and lower limb. CONCLUSIONS: Spasticity has a negative correlation on motor impairment in the upper limb but not in the lower limb. Motor impairment was significantly correlated with grip strength in the upper limb and gait performance in the lower limb of ambulatory stroke survivors.

Higher CD4+CD40+ T cells (Th40 cells) associate with systemic lupus erythematosus activity.

The aim of this study was to investigate the characteristics of CD4+CD40+ T cells (Th40 cells) in Chinese systemic lupus erythematosus (SLE) patients. Flow cytometry was used to identify the percentage of Th40 cells in peripheral blood from 24 SLE patients and 24 healthy individuals and the level of IL-2, IL-4, IL-6, IL-10, IFN-r, and TNF-α in serum (22 cases) from the SLE patients. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) was used to assess the SLE disease active state. The percentage of Th40 cells in T cells from SLE patients (19.37 ± 17.43) (%) was significantly higher than that from healthy individuals (4.52 ± 3.16) (%) (P < 0.001). The percentage of Th40 cells was also positively associated with SLEDAI-2000 (P = 0.001) and negatively associated with complement C3 (P = 0.007). The Th40 cell percentage was different in SLE patients with different organs involved. The Th40 cell percentage in SLE patients with lupus serositis (29.29 ± 22.19) was significantly higher than that in patients without serositis (13.41 ± 10.79; P = 0.040), and the percentage in SLE patients with lupus pneumonia involvement (29.11 ± 11.88) was significantly higher than that in patients without lupus pneumonia (16.80 ± 17.99; P = 0.043). After 4 weeks treatment, the Th40 cell percentage decreased significantly (P = 0.005). However, Th40 cell expression was not related to cytokines (IL-2, IL-4, IL-6, IL-10, IFN-r, and TNF-α; P > 0.05). A significantly higher percentage of Th40 cells was found in SLE patients, and the Th40 cell percentage was associated with SLE activity. Thus, Th40 cells may be used as a predictor for SLE disease activity and severity and therapeutic efficacy.

Strategies to improve the therapeutic efficacy of mesenchymal stem cell-derived extracellular vesicle (MSC-EV): a promising cell-free therapy for liver disease.

Liver disease has emerged as a significant worldwide health challenge due to its diverse causative factors and therapeutic complexities. The majority of liver diseases ultimately progress to end-stage liver disease and liver transplantation remains the only effective therapy with the limitations of donor organ shortage, lifelong immunosuppressants and expensive treatment costs. Numerous pre-clinical studies have revealed that extracellular vesicles released by mesenchymal stem cells (MSC-EV) exhibited considerable potential in treating liver diseases. Although natural MSC-EV has many potential advantages, some characteristics of MSC-EV, such as heterogeneity, uneven therapeutic effect, and rapid clearance in vivo constrain its clinical translation. In recent years, researchers have explored plenty of ways to improve the therapeutic efficacy and rotation rate of MSC-EV in the treatment of liver disease. In this review, we summarized current strategies to enhance the therapeutic potency of MSC-EV, mainly including optimization culture conditions in MSC or modifications of MSC-EV, aiming to facilitate the development and clinical application of MSC-EV in treating liver disease.

China's Gridded Manufacturing Dataset.

The growth of the manufacturing industry is the engine of rapid economic growth in developing regions. Characterizing the geographical distribution of manufacturing firms is critically important for scientists and policymakers. However, data on the manufacturing industry used in previous studies either have a low spatial resolution (or fuzzy classification) or high-resolution information is lacking. Here, we propose a map point-of-interest classification method based on machine learning technology and build a dataset of the distribution of Chinese manufacturing firms called the Gridded Manufacturing Dataset. This dataset includes the number and type of manufacturing firms at a 0.01° latitude by 0.01° longitude scale. It includes all manufacturing firms (classified into seven categories) in China in 2015 (4.56 million) and 2019 (6.19 million). This dataset can be used to characterize temporal and spatial patterns in the distribution of manufacturing firms as well as reveal the mechanisms underlying the development of the manufacturing industry and changes in regional economic policies.

Self-Guided Smartphone Application to Manage Chronic Musculoskeletal Pain: A Randomized, Controlled Pilot Trial.

OBJECTIVE: The goal of this study is to evaluate the feasibility and efficacy of an auricular point acupressure smartphone app (mAPA) to self-manage chronic musculoskeletal pain. METHODS: A prospective, longitudinal, randomized, controlled pilot trial was conducted using a three-group design (self-guided mAPA (n = 14); in-person mAPA (n = 12); and control (n = 11)). The primary outcomes included physical function and pain intensity. RESULTS: After a 4-week APA intervention, participants in the in-person mAPA group had improved physical function of 32% immediately post-intervention and 29% at the 1M follow-up. Participants in the self-guided mAPA group had higher improvement (42% at post-intervention and 48% at the 1M follow-up). Both mAPA groups had similar degrees of pain intensity relief at post-intervention (45% for in-person and 48% for the self-guided group) and the 1M follow-up (42% for in-person and 45% for the self-guided group). Over 50% of the participants in each group reached at least 30% reduced pain intensity at post-intervention, and this was sustained in the mAPA groups at the 1M follow-up. Approximately 80% of the participants in both mAPA groups were satisfied with the treatment outcomes and adhered to the suggested APA practice; however, participants in the self-guided group had higher duration and more frequency in APA use. The attrition rate was 16% at the 1M follow-up. No adverse effects of APA were reported, and participants found APA to be beneficial and the app to be valuable. CONCLUSIONS: The study findings indicate that participants effectively learned APA using a smartphone app, whether they were self-guided or received in-person training. They were able to self-administer APA to successfully manage their pain. Participants found APA to be valuable in their pain self-management and expressed satisfaction with the intervention using the app.