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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Aging after stroke: how to define post-stroke sarcopenia and what are its risk factors?

BACKGROUND: Sarcopenia, generally described as "aging-related loss of skeletal muscle mass and function", can occur secondary to a systemic disease. AIM: This project aimed to study the prevalence of sarcopenia in chronic ambulatory stroke survivors and its associated risk factors using the two most recent diagnostic criteria. DESIGN: A cross-sectional observational study. SETTING: A scientific laboratory. POPULATION: Chronic stroke. METHODS: Twenty-eight ambulatory chronic stroke survivors (12 females; mean age=57.8±11.8 years; time after stroke=76±45 months), hand-grip strength, gait speed, and appendicular skeletal muscle mass (ASM) were measured to define sarcopenia. Risk factors, including motor impairment and spasticity, were identified using regression analysis. RESULTS: The prevalence of sarcopenia varied between 18% and 25% depending on the diagnostic criteria used. A significant difference was seen in the prevalence of low hand grip strength on the affected side (96%) when compared to the contralateral side (25%). The prevalence of slow gait speed was 86% while low ASM was present in 89% of the subjects. Low ASM was marginally negatively correlated with time since stroke and gait speed, but no correlation was observed with age, motor impairment, or spasticity. ASM loss, bone loss and fat deposition were significantly greater in the affected upper limb than in the affected lower limb. Regression analyses showed that time since stroke was a factor associated with bone and muscle loss in the affected upper limb, spasticity had a protective role for muscle loss in the affected lower limb, and walking had a protective role for bone loss in the lower limb. CONCLUSIONS: The prevalence of sarcopenia in stroke survivors is high and is a multifactorial process that is not age-related. Different risk factors contribute to muscle loss in the upper and lower limbs after stroke. CLINICAL REHABILITATION IMPACT: Clinicians need to be aware of high prevalence of sarcopenia in chronic stroke survivors. Sarcopenia is more evident in the upper than lower limbs. Clinicians also need to understand potential protective roles of some factors, such as spasticity and walking for the muscles in the lower limb.

Systematic Analysis of the Grafting-Related Glucanase-Encoding GH9 Family Genes in Pepper, Tomato and Tobacco.

Grafting is an important agricultural practice to control soil-borne diseases, alleviate continuous cropping problems and improve stress tolerance in vegetable industry, but it is relatively less applied in pepper production. A recent study has revealed the key roles of ß-1, 4-glucanase in graft survival. We speculated that the GH9 family gene encoding glucanase may be involved in the obstacles of pepper grafting. Therefore, we performed a systematic analysis of the GH9 family in pepper, tomato and tobacco. A total of 25, 24 and 42 GH9 genes were identified from these three species. Compared with the orthologues of other solanaceous crops, the deduced pepper GH9B3 protein lacks a conserved motif (Motif 5). Promoter cis-element analysis revealed that a wound-responsive element exists in the promoter of tobacco NbGH9B3, but it is absent in the GH9B3 promoter of most solanaceous crops. The auxin-responsive related element is absent in CaGH9B3 promoter, but it presents in the promoter of tobacco, tomato, potato and petunia GH9B3. Tissue and induction expression profiles indicated that GH9 family genes are functionally differentiated. Nine GH9 genes, including CaGH9B3, were detected expressing in pepper stem. The expression patterns of NbGH9B3 and CaGH9B3 in grafting were different in our test condition, with obvious induction in tobacco but repression in pepper. Furthermore, weighted correlation network analysis (WGCNA) revealed 58 transcription factor genes highly co-expressed with NbGH9B3. Eight WRKY binding sites were detected in the promoter of NbGH9B3, and several NbWRKYs were highly co-expressed with NbGH9B3. In conclusion, the missing of Motif 5 in CaGH9B3, and lacking of wound- and auxin-responsive elements in the gene promoter are the potential causes of grafting-related problems in pepper. WRKY family transcription factors could be important regulator of NbGH9B3 in tobacco grafting. Our analysis points out the putative regulators of NbGH9B3, which would be helpful to the functional validation and the study of signal pathways related to grafting in the future.

Cystathionine-ß-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation.

Hyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts as a tumor-suppressive mechanism that must be overcome during transformation. We previously demonstrated that AKT-induced senescence (AIS) is associated with profound transcriptional and metabolic changes. Here, we demonstrate that human fibroblasts undergoing AIS display upregulated cystathionine-ß-synthase (CBS) expression and enhanced uptake of exogenous cysteine, which lead to increased hydrogen sulfide (H2S) and glutathione (GSH) production, consequently protecting senescent cells from oxidative stress-induced cell death. CBS depletion allows AIS cells to escape senescence and re-enter the cell cycle, indicating the importance of CBS activity in maintaining AIS. Mechanistically, we show this restoration of proliferation is mediated through suppressing mitochondrial respiration and reactive oxygen species (ROS) production by reducing mitochondrial localized CBS while retaining antioxidant capacity of transsulfuration pathway. These findings implicate a potential tumor-suppressive role for CBS in cells with aberrant PI3K/AKT pathway activation. Consistent with this concept, in human gastric cancer cells with activated PI3K/AKT signaling, we demonstrate that CBS expression is suppressed due to promoter hypermethylation. CBS loss cooperates with activated PI3K/AKT signaling in promoting anchorage-independent growth of gastric epithelial cells, while CBS restoration suppresses the growth of gastric tumors in vivo. Taken together, we find that CBS is a novel regulator of AIS and a potential tumor suppressor in PI3K/AKT-driven gastric cancers, providing a new exploitable metabolic vulnerability in these cancers.

Research on the evolution and driving forces of the manufacturing industry during the "13th five-year plan" period in Jiangsu province of China based on natural language processing.

The development of China's manufacturing industry has received global attention. However, research on the distribution pattern, changes, and driving forces of the manufacturing industry has been limited by the accessibility of data. This study proposes a method for classifying based on natural language processing. A case study was conducted employing this method, hotspot detection and driving force analysis, wherein the driving forces industrial development during the "13th Five-Year plan" period in Jiangsu province were determined. The main conclusions of the empirical case study are as follows. 1) Through the acquisition of Amap's point-of-interest (POI, a special point location that commonly used in modern automotive navigation systems.) data, an industry type classification algorithm based on the natural language processing of POI names is proposed, with Jiangsu Province serving as an example. The empirical test shows that the accuracy was 95%, and the kappa coefficient was 0.872. 2) The seven types of manufacturing industries including the pulp and paper (PP) industry, metallurgical chemical (MC) industry, pharmaceutical manufacturing (PM) industry, machinery and electronics (ME) industry, wood furniture (WF) industry, textile clothing (TC) industry, and agricultural and food product processing (AF) industry are drawn through a 1 km× 1km projection grid. The evolution map of the spatial pattern and the density field hotspots are also drawn. 3) After analyzing the driving forces of the changes in the number of manufacturing industries mentioned above, we found that manufacturing base, distance from town, population, GDP per capita, distance from the railway station were the significant driving factors of changes in the manufacturing industries mentioned above. The results of this research can help guide the development of manufacturing industries, maximize the advantages of regional factors and conditions, and provide insight into how the spatial layout of the manufacturing industry could be optimized.