SIRT3 alleviates imiquimod-induced psoriatic dermatitis through deacetylation of XBP1s and modulation of TLR7/8 inducing IL-23 production in macrophages.

Current evidence suggests that IL-23, IL-6, and TNF-α play pivotal roles in the pathogenesis of psoriasis. Although it has been established that Sirtuin 3 (SIRT3) mediates the inflammatory process, the underlying mechanisms remain largely unclear. Herein, we substantiated that the inhibition or deletion of SIRT3 increased the acetylation level of spliced form of X-box binding protein 1 (XPB1s), enhancing its transcriptional activity and IL-23a production. Pharmacologically inhibition of XBP1s with MKC8866 downregulated the expression of inflammatory cytokines in SIRT3-inhibited or Sirt3-KO BMDMs stimulated by IMQ. Inhibition or knockdown of SIRT3 could exacerbate psoriasis-like skin inflammation in an imiquimod-induced psoriasis-like mouse model. Besides, a decrease in SIRT3 expression was observed in the macrophages of psoriasis patients, which increased the expression and acetylation level of XBP1s. Overall, we provide compelling evidence of the crucial role of SIRT3 in the IL-23 axis in psoriatic inflammation and novel molecular insights into the anti-inflammatory effects of SIRT3.

Emerging High-Frequency Ultrasound Imaging in Medical Cosmetology.

Cosmetic skin diseases are a part of many dermatological concerns brought up by patients, which negatively affect mental health and quality of life. Imaging technology has an established role in the diagnosis of cosmetic skin diseases by recognizing information on deep skin lesions. Due to the complex physiological and pathological nature of cosmetic skin diseases, the diagnostic imaging performance varies greatly. Developing noninvasive technology models with wide applicability, particularly high-frequency ultrasound (HFUS), which is able to achieve high-resolution imaging of the skin from the stratum corneum down to the deep fascia, is of great significance to medical cosmetology. To explore the great potential of HFUS in cosmetic skin diseases, a narrative review of literature from PubMed and Web of Science published between 1985 and 2022 was conducted. This narrative review focuses on the progression of HFUS imaging in medical cosmetology, especially on its promising application in the quantitative evaluation and differential diagnosis of cutaneous pathological scar, port wine stain (PWS), acne, skin aging, and other cosmetic applications.

Deep convolutional neural network: a novel approach for the detection of Aspergillus fungi via stereomicroscopy.

Fungi of the genus Aspergillus are ubiquitously distributed in nature, and some cause invasive aspergillosis (IA) infections in immunosuppressed individuals and contamination in agricultural products. Because microscopic observation and molecular detection of Aspergillus species represent the most operator-dependent and time-intensive activities, automated and cost-effective approaches are needed. To address this challenge, a deep convolutional neural network (CNN) was used to investigate the ability to classify various Aspergillus species. Using a dissecting microscopy (DM)/stereomicroscopy platform, colonies on plates were scanned with a 35× objective, generating images of sufficient resolution for classification. A total of 8,995 original colony images from seven Aspergillus species cultured in enrichment medium were gathered and autocut to generate 17,142 image crops as training and test datasets containing the typical representative morphology of conidiophores or colonies of each strain. Encouragingly, the Xception model exhibited a classification accuracy of 99.8% on the training image set. After training, our CNN model achieved a classification accuracy of 99.7% on the test image set. Based on the Xception performance during training and testing, this classification algorithm was further applied to recognize and validate a new set of raw images of these strains, showing a detection accuracy of 98.2%. Thus, our study demonstrated a novel concept for an artificial-intelligence-based and cost-effective detection methodology for Aspergillus organisms, which also has the potential to improve the public's understanding of the fungal kingdom.

Molecular targets for anti-oxidative protection of green tea polyphenols against myocardial ischemic injury.

Ischemic heart disease is the leading cause of death worldwide. An improved understanding of the mechanisms involved in myocardial injury would allow intervention downstream in the pathway where certain drugs including natural products could be efficiently applied to target the end effectors of the cell death pathway. Green tea polyphenols (GTPs) have potent anti-oxidative capabilities, which may account for their beneficial effects in preventing oxidative stress associated with ischemia injury. Although studies have provided convincing evidence to support the protective effects of GTPs in cardiovascular system, the potential end effectors that mediate cardiac protection are only beginning to be addressed. Proteomics analyses widely used to identify the protein targets for many cardiovascular diseases have advanced the discovery of the signaling mechanism for GTPs-mediated cardio-protection. This review focuses on putative triggers, mediators, and end effectors for the GTPs-mediated cardio-protection signaling pathways engaged in myocardial ischemia crisis, allowing a promising natural product to be used for ameliorating oxidative stress associated with ischemic heart diseases.

TNF-α-mediated JNK activation in the dorsal root ganglion neurons contributes to Bortezomib-induced peripheral neuropathy.

Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In the present study, we first determined that the administration of BTZ upregulated the expression of TNF-α and phosphorylated JNK1/2 in the dorsal root ganglion (DRG) of rat. Furthermore, the TNF-α synthesis inhibitor thalidomide significantly blocked the activation of both isoforms JNK1 and JNK2 in the DRG and attenuated mechanical allodynia following BTZ treatment. Knockout of the expression of TNF-α receptor TNFR1 (TNFR1 KO mice) or TNFR2 (TNFR2 KO mice) inhibited JNK1 and JNK2 activation and decreased mechanical allodynia induced by BTZ. These results suggest that upregulated TNF-α expression may activate JNK signaling via TNFR1 or TNFR2 to mediate mechanical allodynia following BTZ treatment.

Simultaneous carbon and nutrient removal in an airlift loop reactor under a limited filamentous bulking state.

Airlift loop reactors (ALRs) are important bioreactors for wastewater treatment. However, few studies have investigated the application of an ALR for simultaneous carbon and nutrient removal, especially for activated sludge systems. This study evaluated the performance of integrated nitrogen, phosphorus and COD removal in an ALR with a low height-to-diameter ratio in a limited filamentous bulking (LFB) state (SVI of 180-220mL/g). The average removal efficiencies for COD, NH(4)(+)-N, TN and TP were 91%, 92%, 86% and 94%, respectively. Additional research showed that only under the LFB state, the appropriate distribution of dissolved oxygen inside the ALR was established to promote a well-balanced aerobic and anoxic/anaerobic state. In addition, the macro-gradient of the substrate concentration at the inlet and the heavier bio-P sludge density compensated for the proliferation of filaments. Hence, the stable LFB state was achieved by balancing the floc-forming bacteria and the filamentous bacteria in the ALR.