Targeted protein degradation technology can achieve the modulation of undruggable proteins. Abnormal activation of cyclins can promote tumorigenesis and tumor progression. However, cyclins regard to be undruggable with no small-molecule binders had been released. Here, we utilize hydrophobic tag (HyT)-based small-molecule degraders induced degradation of cyclin T1 and its corresponding kinase partner CDK9. We describe the discovery of a series of novel dual degraders of CDK9-cyclin T1. LL-CDK9-12 demonstrated the most potent and selective degradation ability, with DC50 values of 0.362 μM against CDK9 and 0.680 μM against cyclin T1. In prostate cancer cells, LL-CDK9-12 showed enhanced anti-proliferative activity than its parental molecule SNS032. Moreover, LL-CDK9-12 suppressed the downstream signaling of CDK9 and AR efficiently. Altogether, LL-CDK9-12 was an effective dual degrader of CDK9-cyclin T1 and could be useful in studying the unknown function of CDK9-cyclin T1. Our data also suggest that HyT-based degraders could be used as a strategy to induce the degradation of protein complexes that containing undruggable proteins such as cyclins.

Recently, blockchain-based IoT solutions have been proposed that address trust limitation by maintaining data consistency, immutability, and chronology in IoT environments. However, IoT ecosystems are resource-constrained and have low bandwidth and finite computing power of sensor nodes. Thus, the inclusion of blockchain requires an effective policy design regarding consensus and smart contract environments in heterogeneous IoT applications. Recent studies have presented blockchain as a potential solution in IoT, but an effective view of consensus and smart contract design to meet the end application requirements is an open problem. Motivated by the same, the survey presents the integration of suitable low-powered consensus protocols and smart contract design to assess and validate the blockchain-IoT ecosystems. We discuss the key blockchain concepts and present the scalability and performance issues of consensus protocols to support IoT. Further, we discuss smart contract vulnerabilities and blockchain attacks. Open issues and future directions are presented, supported through a case study of low-powered consensus protocol design in the blockchain- IoT ecosystem. The survey intends to drive novel solutions for future consensus and safe, smart contract designs to support applicative IoT ecosyst

Electrochemical conversion of NO3- to NH3 production is of great environmental significance for water pollution treatment and can artificially close the nitrogen cycle. However, direct nine proton and eight electron transfer leads to low Faraday efficiency (FE) and yield. Herein, the single copper site immobilized on N, P co-doped carbon substrates (Cu-N4/P) was prepared for efficient NO3–to-NH3 conversion. Benefiting from electronic redistribution of Cu site induced by the introduction of the less electronegative element P, Cu-N4/P catalyst has superior catalytic properties to the comparison sample, including 100% NO3- conversion, high FE (96.12%) and NH3 yield (124.22 mmol/(h·gcat)). Density functional theory (DFT) explains the effective operation mechanism that P doping can promote the spontaneous hydrogenation of *NO to form *NOH, thus promoting the formation of NH3 from NO3- reduction reaction. The heteroatom doping strategy mentioned proposes a new approach for promoting NO3–to-NH3 conversion at atomic level catalytic sites.

Non-albicans Candida (NAC) species are emerging causes of all Candidemia infections, but relatively less is known about the immune responses induced by these species. In this study, we compared the ability of cytokine production by human peripheral blood mononuclear cells (PBMC) upon stimulation with different Candida species. We measured secreted cytokines by ELISA and checked the functional profile of T cell responses at a single-cell level by multi-color flow cytometry technique. Though there was a differential expression of cytokines against the Candida species, a significant difference was observed in the levels of IFN-γ, TNF-α, IL-10, IL-12p40, and IL-23 (p<0.05) between the Candida species. There is a significant difference was observed between C. albicans and C. glabrata (p-0.026) in the levels of TNF-α. C. glabrata showed significant difference with C. albicans, C. parapsilosis and C. krusei in the levels of IL-10. Despite the percentages of CD4+ and CD8+ expressing Th1, Th2 and Th17 cytokines being higher in stimulated PBMC, none of the Candida species showed significant differences. The levels of secreted IL-17A and IL-23 were consistently lower in Candida species regardless of the stimulus used. Here we showed the differential regulation of the Th1, Th2 and Th17 during Candida species stimulation of the immune system in vitro. Our results also indicate that while C. albicans induces a Th1 response, C. glabrata induces Th2 cellular responses. This study could enhance our knowledge of differential immune responses induced by Candida species and may help to develop immunotherapeutics and vaccines.

Background: Following the worldwide mass vaccination to prevent and protect the child population from the deadly virus, on 17th May 2021, the Primary Health Care Corporation (PHCC), Qatar launched the BNT162b2 COVID-19 vaccine campaign among adolescents i.e., 12 to 15 years of age across region through all 27 health centers. We estimated the safety and protective efficacy of the BNT162b2 COVID-19 vaccine among the vaccinated and non-vaccinated adolescent population in Qatar. Methods: A quantitative retrospective observational study assessed the medical records of SARS-COV-2 positive adolescents (12-15 years) of all 27 Primary Healthcare Centres of PHCC. All data were obtained during the second wave of the SARS-COV-2 pandemic from 17 th June 2021 to 17 th December 2021. Results: The study data involved 1956 SARS-CoV-2 infection (RTPCR positive) cases. Out of 1956 children, 20.55% were vaccinated (n=402) and 79.45% were non-vaccinated (n=1554). The mean age for the vaccinated group was 13.89 ± 0.93 and non-vaccinated group was 12.99 ± 0.93. The number of vaccinated participants 20.55% (n=402) of the total sample size who contracted SARS-CoV-2 infections was significantly lesser compared to the non-vaccinated population 79.45% (n=1554). Incidence of the SARS-COV-2 infection was found to be statistically significant among the vaccinated group who received 2 doses of Pfizer-BioNTech vaccine (p-value<0.001) rendering the vaccine effectiveness against prevention of the SARS-CoV-2 infections. Conclusion: In summary, our findings indicate that protection of Pfizer BioNTech (BNT162b2) COVID-19 vaccine against SARS-CoV-2 infections is satisfactory as only one-fifth of the total study population contracted SARS-CoV-2 infections after the double dose regimen. Our findings support the importance of maximizing vaccination coverage for considering booster doses for adolescents to enhance protection. Further studies will be needed to assess the duration of protection and immune-prophylactic response and the need for booster doses.

Background: Few studies have investigated the efficacy of comprehensive therapy, including immunotherapy, for gastric cancer with synchronous liver metastases (GCLM). We compared the effect between immunochemotherapy and chemotherapy alone as a conversion therapy on the oncological outcomes of patients with GCLM. Methods: Clinicopathological data of 100 patients with GCLM from February 2017 to October 2021 from our institution were retrospectively analyzed. The patients were divided into immunochemotherapy (n=33) and chemotherapy alone groups (n=67). Results: The baseline clinicopathological data did not significantly differ between two groups. The immunochemotherapy group had higher overall response (59.4% vs. 44.0%, P=0.029) and disease control rates (71.9% vs. 49.2%, P=0.036) than the chemotherapy group. The immunochemotherapy group showed better tumor regression in gastric mass, metastasis lymph nodes, and liver lesion than did the chemotherapy group. Ten (30.3%) patients in the immunochemotherapy group and thirteen (19.4%) in the chemotherapy group underwent surgery after conversion therapy. However, the difference was not significant. The overall survival (OS) and progression-free survival (PFS) rates were better in the immunochemotherapy group than in the chemotherapy group. Treatment-related adverse events occurred in 24 (72.7%) and 47 (70.1%) patients in the immunochemotherapy and chemotherapy groups, respectively. Conclusions: As a conversion therapy for GCLM, immunotherapy yielded better primary and metastatic tumor regression and survival benefit, with no increase in adverse events than did chemotherapy.

High levels of effortful control have been shown to protect children from negative health outcomes following early adversity. In this study, we tested whether effortful control already moderates the effects of parenting stress on children’s cortisol levels in toddlerhood. In 31 families, parental reports of parenting stress and toddlers’ effortful control were obtained via questionnaires, and toddlers’ salivary cortisol levels were assessed twice in the morning and once in the evening. Contrary to expectations, parenting stress was not related to toddlers’ cortisol levels, and effortful control did not moderate these non-significant associations. Higher levels of parenting stress were related to lower levels of toddler’s effortful control (r = -.43, p =.016). Future work may examine at what age effortful control starts to influence an individual’s psychobiological adaptation in the context of (parenting) stress, which may inform prevention and intervention approaches.

Substance exposed newborns (SENs) are at risk of developmental delay(s). Early intervention (EI) access, key to addressing these risks, is inequitable. Objectives were to determine prevalence of EI referral in the Colorado Hospitals Substance Exposed Newborn (CHoSEN) Quality Improvement Collaborative (USA) and evaluate predictors of referral. Maternal-infant dyads with exposure to medications for opioid use disorder (MOUD), illicit/prescription opioids, and/or non-opioid substances were included. Chi-square, Fisher’s exact, and ANOVA tests evaluated differences in maternal/infant characteristics by referral. Multivariable logistic regression models assessed the independent association of characteristics with referral. Among 991 primarily White, non-Hispanic dyads, 407 (41.1%) SENs received EI referral. Infants born to mothers with non-MOUD (AOR 0.22, 95% CI 0.10, 0.45) and polysubstance (AOR 0.60, 95% CI 0.36, 0.98) exposure were less likely to receive referral compared to infants born to mothers with MOUD exposure. Those with shorter length of stay of 1-3 days (AOR 0.03, 95% CI 0.01, 0.07) and 4-6 days (AOR 0.47, 95% CI 0.32, 0.69) were less likely to receive referral compared to infants admitted >6 days. Less than half of identified SENs received EI referral with variation by substance exposure and length of stay. Systems to ensure equitable access to services are crucial.

Objectives: We aimed to evaluate the efficacy of GeneXpert MTB/RIF Ultra (Ultra) for the early diagnosis of tuberculous meningitis (TBM). Methods: Seventy-nine patients were analyzed. Mycobacterium tuberculosis was measured in the cerebrospinal fluid (CSF), using Ultra, GeneXpert MTB/RIF (Xpert), Metagenomic Next-Generation Sequencing (mNGS), and Mycobacteria Growth Indicator Tube (MGIT) assays. The detection performance and rifampicin drug sensitivity of each method were analyzed based on clinical diagnoses. Results: The sensitivity (56.4%), area under the curve (AUC, 0.782), and Kappa value (0.521) of Ultra were higher than the sensitivity, AUC, and Kappa value of MGIT (20%, 0.600, 0.236), Xpert (40%, 0.700, 0.236), and mNGS (32.7%, 0.664, 0.352). In the 31 Ultra positive cases, 24 were rifampicin susceptible, and 7 were rifampicin indeterminate. Conclusion: The Ultra assay detected Mycobacterium tuberculosis in CSF with higher sensitivity, compared with other assays. Thus, the Ultra test can be used for the early diagnosis of TBM.

Moorlands dominated by Calluna vulgaris (hereafter Calluna) are globally rare and under increasing threat of wildfires due to climate change. The soil seed bank is important for community resilience, but research on its contribution to regenerating vegetation after moorland fires has to date focused on prescribed fire or on the short-term (≤ 2 year) impacts of wildfire. To address the role of the seed bank in long-term vegetation regeneration, we studied a chronosequence of six wildfire sites within a Scottish moorland catchment, ranging from 2 to 64 years since burning. We recorded vegetation composition and sampled the seed bank. Calluna and Erica spp. comprised 66 % and 27 % of germinated seeds, respectively, and the majority of vegetation species were not represented in the seed bank. Canonical Correspondence Analysis (CCA) revealed that time since fire was a strong predictor of vegetation species composition, but it had no effect on seed bank composition, suggesting that the same species dominate the seed bank regardless of burning. Whilst total seed density was marginally reduced after wildfire and slightly increased with time, the non-Calluna seed bank was more notably affected. The proportion of non-Calluna species decreased with time in both vegetation and seed bank as Calluna cover was re-established and the seed bank of other species became gradually depleted. Whilst relative non-Calluna cover in the vegetation was at a maximum at the start of the chronosequence and then declined, the proportion of non-Calluna in the seed bank followed a unimodal pattern after fire and reached a peak after around 35 years. Our results contribute to the knowledge of how moorland ecosystems regenerate after severe disturbances, which are likely to become more common as the climate changes.

Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis and rational therapeutics. A microarray-based comparative transcriptomic analysis was performed to elucidate the molecular mechanisms of BS and identify any potential therapeutic targets. Twenty-nine BS patients (B) and 15 age and sex-matched control subjects (C) were recruited. Patients were grouped as mucocutaneous (M), ocular (O), and vascular (V) according to their clinical phenotypes. GeneChip Human Genome U133 Plus 2.0 arrays were used for expression profiling on peripheral blood samples of the patients and the control subjects. Following documentation of the differentially expressed gene (DEG) sets, the data were further evaluated with bioinformatics analysis, visualization, and enrichment tools. Validation of the microarray data was performed using qRT-PCR. When P ≤0.05 and fold change ≥2.0 were chosen, the following numbers of DEGs were obtained; B vs. C: 28, M vs. C: 20, O vs. C: 8, V vs. C: 555, M vs. O: 6, M vs. V: 324, O vs. V: 142. Venn diagram analysis indicated only two genes, CLEC12A and IFI27, in the intersection of M vs. C and O vs. C and V vs. C. Another noteworthy gene appeared as CLC in the DEG sets. Cluster analyses successfully clustered distinct clinical phenotypes of BS. While innate immunity-related processes were enriched in the M group, adaptive immunity-specific processes were significantly enriched in the O and V groups. Distinct clinical phenotypes of BS patients displayed distinct expression profiles. In Turkish BS patients, expression differences regarding the genes CLEC12A, IFI27, and CLC seemed to be operative in the disease pathogenesis. Based on these findings, future research should consider the immunogenetic heterogeneity of BS clinical phenotypes. Two anti-inflammatory genes, namely CLEC12A and CLC, may be valuable as therapeutic targets and may also help design an experimental model in BS.

The widespread use of networked, intelligent, and adaptable devices in various domains, such as smart cities and home automation, climate control, manufacturing and logistics, healthcare, education, and agriculture, has been hastened by recent developments in hardware and software technologies. In all these application domains, the concept of the Internet of Things ( helps to achieve process automation and decrease labor costs. One such subdomain is IoT Forensics which involves Digital Forensics concerning IoT devices, networks, or clouds. In this process of obtaining substantial evidence from the devices, networks, or cloud, a large amount of data and operations on said data are involved. Hence, looking through IoT Forensics through the methodology dealing with data, known as Data Analytics, is essential. This paper presents an interpretation of IoT Forensics from the standpoint of Data Analytics. To explain the same in detail, the paper focuses on IoT Forensics, its methodologies, and how they relate to data analytics stages. Towards the end, the paper discusses current developments in IoT forensics from the Data Analytics perspective, limitations observed in the existing technologies, adoption challenges, and possible future advancements.

Introduction: Probiotics are live microorganisms that, when administered in appropriate colonies, can delay the destruction of the immune system and contribute to the maintenance of immunity in HIV patients. Probiotics play an important role in stimulating natural killer T cells, strengthening the functional gut barrier, and reducing systemic inflammation. Methods: This study was a randomized double blind clinical trial involving 30 patients treated with ART who had experienced immunological failure despite HIV viral suppression. Patients were divided into two equal groups of 15, the first group received 2 probiotic capsules daily with a colony count of 10⁹CFU per capsule containing seven strains ,after three months they were examined for CD4+ counts by flow cytometry, after a one month washout period the participants who had received probiotics were switched to placebo, and the participants who had received placebo were given probiotics for three months, and they were examined for CD4+ counts seven months after the start of the study. Results: In the first group, administration of the placebo resulted in a decrease in CD4 count in the first three months (from 202.21 to 181.79, p-value < 0.001),which may be due to the natural history of the disease. After probiotics administration, CD4 count increased significantly (from 181.79 to 243.86, p-value < 0.001). Overall, after 7 months of study, there was a significant increase in the mean CD count from 202.21 to 243.86 (p-value < 0.001). In the second group, administration of probiotics in the first three months of the study resulted in a significant increase in the mean CD4 count (from 126.45 to 175.73, p-value < 0.001).Termination of treatment with probiotics resulted in a significant decrease (from 175.73 to 138.9, p-value < 0.001)but overall the CD4 count at the end of the study was significantly higher than at baseline (p-value < 0.001).

Euploca wightiana P. Javad & A. A. Ancy sp. nov., a new species of the family Heliotropiaceae is described from Coimbatore district of South India. Morphologically it is similar to Euploca marifolia but differs in being perennial; erect woody stem with dense hirsute hairs; oblong leaves with obtuse apex; inflorescence with distantly placed flowers; long, cylindrical style with unifid, capitate stigma and densely hirsute nutlets. The species remained misidentified in herbaria for long. Detailed description, photo plates and distribution maps are provided. Morphological differences with relevant species are discussed. The status of the new species is provisionally assessed here as ‘endangered’ according to IUCN Red List Categories and Criteria.

Saxifraga cataphracta, a new species of Saxifragaceae from Southwest China, is described and illustrated. Morphological and molecular evidence (matK, psbA-trnH, psaJ-rpl33) indicate that S. cataphracta belongs to S. sect. Irregulares, and closely related to S. geifolia and S. mengtzeana. The new species can be diagnosed by its leaf blade abaxially with white or virescent interveinal streaks, involucre and bracts conspicuous, capsule beaks winged when mature.

Background: Growing evidence suggests that the KLHL family may be involved in the occurrence and development of cancer. KLHL38, a member of the KLHL protein family, contains BTB/POZ, BACK domains, and five to six Kelch motifs. However, no pan-cancer analyses have been conducted on KLHL38. In this study, we aimed to explore the potential biological functions of KLHL38 that may provide potential tumor-related therapeutic targets. Methods: The potential roles of KLHL38 in different tumor types were explored based on The Cancer Genome Atlas (TCGA), Genotype-tissue expression (GTEx), Tumor Immune Estimation Resource (TIMER), and Gene Set Enrichment Analysis (GSEA) datasets. Several factors related to KLHL38 were analyzed, including expression differences, survival, pathological stage, DNA methylation, tumor mutation burden (TMB), tumor microenvironment (TME), stemness score, and immune cell infiltration. Results: There were significant differences in KLHL38 expression among different cancer types and between cancer tissue and normal tissue, which was closely correlated with survival prognosis. Furthermore, KLHL38 expression was found to be correlated with DNA methylation, tumor mutations, and stemness scores in major cancer types, suggesting its involvement in cancer development. To some extent, KLHL38 expression levels were significantly correlated with immune cell infiltration, immune checkpoint genes, and immune regulatory genes. These results indicated that KLHL38 can be used as a tumor prognostic indicator. Conclusion: In our study, we analyzed the role of KLHL38 role in tumor development and immunotherapy, which may provide a potential new target for tumor treatment.

The objective of this study is to describe and correlate the development areas of premature children and to verify the influence of sociodemographic factors. This is a cross-sectional study with a quantitative approach, conducted with 79 premature children aged from 15 days to 42 months old. The sociodemographic questionnaire and the Bayley III Scale were used. The participants’ performance fell within the expected parameters in the weighted and composite score and percentile in all the domains evaluated. However, nearly 39% did not achieve full acquisition in sensory processing and 50.6% presented at least one statistically significant discrepancy when comparing two development areas. The analysis performed and the set of results obtained were considered relevant for constituting a risk indicator for childhood development that can go unnoticed in healthy preterm infants, hindering early intervention and leaving them vulnerable to difficulties throughout life.

During a cold La Niña period (August 2007-January 2008) in the central Galápagos archipelago, 70% of Pocillopora finger corals were bleached across three long-term monitoring sites, affording an opportunity to examine the impact of El Niño Southern Oscillation-related temperature anomalies on the persistence of these corals and their associated community of fish and mobile macroinvertebrates. Using a time series empirical approach, we tagged and tracked the fate of 96 coral heads and their associates. When surveyed in July 2008, live (recovered) and dead corals supported similar levels of randomized observed species richness and Chao 1 estimated species richness. Whereas richness on the surviving live corals remained fairly stable, Chao 1 estimated richness on dead corals underwent a nearly 50% increase between July and January 2009, thereafter declining to 50% of originally surveyed richness by February 2010. This nonlinear change in species richness was largely due to influx and decline in opportunistic generalists including pencil urchin bioeroders, gastropod snails, and hermit crabs that colonized dead corals and fed on sessile invertebrates and algae that had initially recruited to dead and undefended coral substrate. Thus, dead corals retained high overall species richness until live corals had recovered; after which richness declined as dead corals eroded and disappeared (July 2011). Live corals attracted a less speciose but stable assemblage of mutualistic xanthid crabs and fishes that increased in abundance over time with the recovery and growth of live coral tissue. Overall, three physical features of the finger coral habitats (coral vital status, total surface area, and maximum branch length) predicted the number of species associated with each colony. The delayed diversity loss of associated species following La Niña disturbance to a foundation species represents a local extinction debt of 32-49-month duration. A better understanding of the scale of extinction debt in foundational marine ecosystems is needed to quantify the breadth of impacts of climate oscillations on biodiversity and ecosystem functioning.

Onosma safaie-fari (in subsect. Asterotricha) is described and introduced as new species from Kurdistan province. O. safaie-fari morphological similar to O. qandilica, however, it is seperated by sterile shoot and cauline leaves shape; fruiting calyx length, calyx lobes shape and width, corolla length, corolla color and anthers length. Also Onosma safaie-fari closed to O. bisotunensis but it is differentiated by sterile shoot and cauline leaves shape, lower bract shape and length; length of fruiting calyx; corolla color and length; free part of filaments length, position of filaments arising from corolla and anthers length.

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Two new species from Iran was described in this study. Fritillaria shehbazii from Western Azerbaijan province in northwest Iran and F. selenica from Kurdistan province in western Iran. F. shehbazii is similar to F. chlororhabdota, F. pinardii, F. kordestanica and F. assyriaca in the F. caucasica group in general facies but differs mainly by the color and size of its lowest leaves, shape and colour of perianth segments. F. selenica is similar to F. avromanica and F. assyriaca in general facies but differs mainly by narrower leaves and color of perianth segments. Detailed taxonomic descriptions, diagnostic characteristics, illustrations, original photographs, geographical distributions, habitat, phenology and ecology, etymology, conservation status, and identification key of the new and the related species are presented in this study.

Background: Patients with human immunodeficiency virus (HIV) are at a significantly higher risk of cardiovascular disease (CVD) compared to HIV-negative people. Left heart dysfunction is the most common cardiac complication in people living with HIV/AIDS (PLWHA), and diastolic dysfunction is an important predictor of cardiovascular events. The aims of this study were 1) to detect changes in left cardiac structure and function in antiretroviral therapy (ART)-naive PLWHA using echocardiography; and 2) to investigate the risk factors for the development of left ventricular diastolic dysfunction (LVDD) in ART-naive PLWHA. Methods: We retrospectively included 105 ART-naïve PLWHA and included 90 healthy subjects as controls to compare the differences in left heart structure and function between the two groups. Univariate and multifactorial logistic regression were employed to explore the risk factors of the development of LVDD in ART-naive PLWHA. Results: The left ventricular end-diastolic internal diameter (LVEDD), left ventricular mass index (LVMI), and left atrial volume index (LAVI) were significantly greater in PLWHA than in controls (p＜0.05). The E/A ratio, lateral e’ velocity, and mitral deceleration time (DT) were significantly lower in PLWHA than in controls (p < 0.05). Average E/e’ ratio was significantly higher in PLWHA than in controls (p < 0.05). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were not significantly different between PLWHA and controls (p＞0.05). Multifactorial logistic regression analysis showed that age, body mass index (BMI), and CD4+ count < 200 cells/μL were independent influencing factors for LVDD in ART-naive PLWHA (OR=1.781, 1.228, 3.683, p＜0.05). Conclusions: Left ventricular systolic function did not differ between PLWHA and controls, and left ventricular diastolic function was lower in PLWHA than in controls. Age, BMI, and CD4+ count were independent factors affecting LVDD in ART-naive PLWHA.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that can lead to joint deformity and severe disorders, as a basic pathological change in articular rheumatism, joint tenderness and progressive destruction, arthritis and panusis.At present, the specific etiology of articular rheumatism is still unknown.The imbalance of immune homeostasis is the root cause of rheumatoid arthritis.In research, the hippocampal signaling pathway, which is widely expressed in various cell lines, plays an important role in maintaining immune homeostasis and may be involved in the pathogenesis of rheumatoid arthritis.In this study, in order to provide new ideas for understanding the pathogenesis mechanism of articular rheumatism, the research progress of the hippo signal transduction pathway and its main members involved in the crisis of RA is outlined from the three sides of the regulation and maintenance of the autoimmune homeostasis, the promotion of the pathogenicity of the synovial fibroblast and the regulation of the osteoclast differentiation.

Unbalanced number of samples is a key problem that restricts the practical application of Convolutional Neural Networks (CNNs) in the field of wind turbine gearbox fault diagnosis. To solve this problem, here, a method based on two-dimensional spectrogram and improved Generative Adversarial Networks (GANs) is proposed to enhance the unbalanced data of wind turbine gearbox categories. First, the original one-dimensional vibration signal is converted into a two-dimensional spectrogram. Based on the two-dimensional Conditional GANs (2D-CGANs), the labels are input into the generation network and the discriminant network by means of projection, and a sample enhancement model is established, thereby generating multi-working conditions, multi-type and high-quality pseudo-fault samples. Second, the sample set is balanced by the sample augmentation model to train a fault diagnosis model based on CNNs. Finally, the method is verified from three aspects: the training process of the sample enhancement model, the generation ability, and the diagnosis ability of the fault diagnosis model. The results show that the proposed method can generate diverse and high-quality 128×192 resolution pseudo-fault samples, effectively improving the fault identification accuracy and network training speed, with strong generalization, and have good engineering application feasibility.